674 replies to this topic

[Turnbuckle]

In cerebrospinal fluid the concentration of amyloid-β protein Aβ42 is not correlated with age, while tau protein appears to increase exponentially at a rate similar to mortality. This finding suggests that emphasis needs to be placed on clearing tau protein and addressing the underlying cause of its increase.

 

“Tau and Aβ42 in Cerebrospinal Fluid from Healthy Adults 21–93 Years of Age: Establishment of Reference Values” (2001) http://clinchem.aacc...ent/47/10/1776 

 

 

Your reference is for healthy people. In this thread I accepted the hypothesis that Aβ and tau cooperate in a feedback loop, but that it starts with Aβ. This is consistent with the strong genetic link between Aβ and AD with APOE4. See the first reference link in the first post of this thread. 

[tolerant]

Hi everyone,

 

First of all, thank you all, and in particular Turnbuckle, for this thread. I have been in terrifying cognitive decline for the past 14 months. Even reading and writing on here is hard. When someone referred to there being another thread or other protocols with respect to AD, it was too much for my brain to handle. I can only follow very simple instructions, and thankfully OP has provided just that. I think there was a reference in this thread to an "emergency protocol", i.e. something to get the person to the level where they can do their own research and experimentation. This is what I need right now, and I understand the protocol posted by OP is that emergency remedy. Please correct me if I'm wrong.

 

There are a number of questions that I can think of right now.

 

1. Did people find that HEPPS purchased on Amazon would not ship a residential address? Were there any issues with customs?

 

2. I live in Australia and the two sellers of HEPPS on Amazon don't ship to here, so I was going to use a package forwarding company such as Shipito, and I want to alert other members of this service.

 

3. Does the "European" group buy for HEPPS mean that only people in Europe can take part?

 

4. I am not at all certain that I have AD. It's just a possibility. Would it be safe/useful to use the OP's protocol even if it turns out that I don't have AD? Yesterday, when I discovered this thread, I also learned that there are scans (PET I think) that can tell whether or not a person has amyloid beta plaques. I will try to have this scan done.

 

Thanks!

 

P.S. It is strange that when you search Amazon for HEPPS, you get nothing. How were people even able to find the two HEPPS sources?

Edited by tolerant, 16 September 2018 - 03:08 AM.

[tolerant]

A few more questions if I may:

 

5. With carnosine powder, I can only find it unbranded or brands that I haven't heard of, i.e. not the major brands. Do you think it's the real deal or should I just stick with 500 mg capsules (which are not that much more expensive than the powder)?

 

6. I am about to start HGH with the hope that it will ease my debilitating and treatment-resistant depression and anxiety and improve my cognition. What do people think of that? Is it compatible with OP's stack? What effects can it have on dementia or other forms of cognitive impairment?

[Empiricus]

Tolerant, You say you're about to start HGH, yet you're worried about safety of consuming items in this protocol!? That makes no sense. You should be asking why HGH justifies the risk.   As for the protocol, I had taken everything in it (except for HEPPS) many times in the past, as have thousands of consumers of health supplements.  As for HEPPS, the main thing is not to confuse it with with another chemical of a similar spelling (one "p").  

 

You can waste a lot of time/money on testing that will not actually prove you don't have anything.  On the other hand, Turnbuckle's protocol is diagnostic.  If it helps, you will know what your problem was.  

 

I would definitely contact the guy doing the European buy as it's going to be your most cheap option. In the meantime, why not start the protocol, using taurine (which is molecularly similar to HEPPS)?   

Edited by Empiricus, 16 September 2018 - 07:32 AM.

[tolerant]

Empiricus,

 

Where did I say that I am concerned about the safety of the protocol? I'm not concerned in the slightest. I am concerned somewhat by HGH though, so I was asking for input on that. I have already ordered HEPPS from Amazon, along with every other item on the protocol. HEPPS, along with dihydromyricetin, carnosine, and hydroxytyrosol will arrive later than the rest, as I'm using a package forwarding service. The rest I bought on iHerb, so I should have it in a few days. Can I start the protocol without dihydromyricetin? I thought it was a primary ingredient, just as MB was in the previous protocol. Is this correct?

 

I think another very important question I should have asked is even if this protocol doesn't help me with my symptoms, is it useful as a preventive tool?

 

Thanks for your input!

[Empiricus]

"Would it be safe/useful to use the OP's protocol...."  

[tolerant]

"Would it be safe/useful to use the OP's protocol...."  

 

OK. I see what you mean. When I say I'm not concerned by the safety of the protocol, I mean the individual substances of the protocol. True, I've never heard of HEPPS or dihydromyricetin before, but dihydromyricetin is a flavanolol, so no issues there, while HEPPS does come across as a little concerning because it's some sort of chemical used as a buffer (whatever that means), but since people in this thread are using it, then it must be fine. Also, my cognitive symptoms are so debilitating that I would be willing to try anything, really. 

 

So by safety, I guess I mean that if I definitely don't have AD, is it safe to fix something that ain't broke, i.e. to mess around with things I have zero understanding of.

 

P.S. I would also very much like to avoid my symptoms getting worse during the first few days because it would cause great anxiety. I take it that the way to do it is to slowly build up the dose of HEPPS/taurine?

Edited by tolerant, 16 September 2018 - 07:53 AM.

[tolerant]

Another question I have is how do I know if I have herpes? Is it always visible on the outside?

[aribadabar]

Another question I have is how do I know if I have herpes? Is it always visible on the outside?

 

If you've ever had several bouts of cold sores chances are you are among the 80%+ of the people worldwide that are carrying the HSV-1 virus permanently so I'd operate out of the premise that you do have it - it is just in latency state until it is activated the next time by some of the triggers which result in cold sores as external manifestation.

[Turnbuckle]

A link to the full AD/herpes paper-- https://sci-hub.tw/1...ron.2018.05.023

 

Note that this Russian site is continually being taken down by governments.

[Turnbuckle]

Hi everyone,

 

First of all, thank you all, and in particular Turnbuckle, for this thread. I have been in terrifying cognitive decline for the past 14 months. Even reading and writing on here is hard. When someone referred to there being another thread or other protocols with respect to AD, it was too much for my brain to handle. I can only follow very simple instructions, and thankfully OP has provided just that. I think there was a reference in this thread to an "emergency protocol", i.e. something to get the person to the level where they can do their own research and experimentation. This is what I need right now, and I understand the protocol posted by OP is that emergency remedy. Please correct me if I'm wrong.

 

There are a number of questions that I can think of right now.

 

1. Did people find that HEPPS purchased on Amazon would not ship a residential address? Were there any issues with customs?

 

2. I live in Australia and the two sellers of HEPPS on Amazon don't ship to here, so I was going to use a package forwarding company such as Shipito, and I want to alert other members of this service.

 

3. Does the "European" group buy for HEPPS mean that only people in Europe can take part?

 

4. I am not at all certain that I have AD. It's just a possibility. Would it be safe/useful to use the OP's protocol even if it turns out that I don't have AD? Yesterday, when I discovered this thread, I also learned that there are scans (PET I think) that can tell whether or not a person has amyloid beta plaques. I will try to have this scan done.

 

Thanks!

 

P.S. It is strange that when you search Amazon for HEPPS, you get nothing. How were people even able to find the two HEPPS sources?

 

I have posted several protocols for various ailments of aging and when asked which should be done first, I said that AD should be treated as an emergency situation and done first, while the others can be done at your leisure. Like all the others, this AD protocol has evolved in an iterative fashion, but a link can always be found to the latest protocol on my profile page--click on my avatar or here.

 

HEPPS will ship to residential US addresses when ordered thru Amazon in the US, but it is not offered thru Amazon international, and not in Australia, Canada, Britain, or any other countries I know of. Searching for it on those sites will not show it. You'll only find it on the US site.

 

If you don't actually have AD, this protocol shouldn't hurt. It simply won't work. If you do get a PET scan done before and after, that will be very interesting. The cost of a PET scan in the US ($3,000 on up) is prohibitive for most, while the protocol itself is cheap.

Edited by Turnbuckle, 16 September 2018 - 01:26 PM.

[theobromananda]

 

Does the "European" group buy for HEPPS mean that only people in Europe can take part?

 

I'd be willing to ship to Australia, but I am not sure how much shipping will be, nor do I know the import customs.

 

Send me a message with the amount required if you are interested.

[tolerant]

If you've ever had several bouts of cold sores chances are you are among the 80%+ of the people worldwide that are carrying the HSV-1 virus permanently so I'd operate out of the premise that you do have it - it is just in latency state until it is activated the next time by some of the triggers which result in cold sores as external manifestation.

 

Thanks, I ordered the lysine.

[tolerant]

I'd be willing to ship to Australia, but I am not sure how much shipping will be, nor do I know the import customs.

 

Send me a message with the amount required if you are interested.

 

Thanks, theobromanada, but I've already ordered from Amazon. Should be arriving on Monday.

 

I want to note, especially for people who suffer from anxiety, that taurine acts basically like a benzodiazepine, and taking large amounts for protracted periods may result in addiction and withdrawal symptoms when you discontinue. It's discussed in the massive anxiety thread: https://www.longecit...ly-effectively/

 

I also have a few questions as follows:

 

1. As I understand it, amyloid beta plaques accumulate throughout a person's lifetime. So would I be right in assuming that someone around 40 would already have these plaques, and using the dissolving substances without detoxification is a good diagnostic test as to what extent you have the plaques, i.e. if you feel cognitive impairment from HEPPS and taurine alone, then you do have a substantial amount of plaques?

 

2. Should all the substances in the revised protocol be taken at together at the same time?

 

Thanks!

[Empiricus]

I'm familiar with that thread, it scared me when I first read it, but mainly I think on account of all the red font, not so much the content. 

 

Concerning taurine and anxiety, none of the studies quoted seem particularly alarming, some in fact, seem reassuring. Moreover, the experiential reports on that thread are also reassuring, and collaborate my experience with taurine. For example, https://www.longecit...10#entry525507 

 

That thread raises the question, what is the function of taurine?  The OP on that thread is narrowly focused on how everything effects GABA, as if that is the most important question with respect to everything mentioned, including taurine.

 

Edited by Empiricus, 22 September 2018 - 05:10 AM.

[bladedmind]

Tried my first round,  15 mg of taurine way too much for me, groggy and dozing all next day.  Otherwise felt good.  My aged (69) nerves were tingly in a pleasant way.  

 

I don't know biochemistry, so please let me pose a question.   Would homotaurine work better than taurine?  Especially for APOE 4/4s?  Or does HEPPS serve the same purpose as homotaurine?   Homotaurine can be bought online from Canada and UK, and one of the vendors is less pricy than the others. 

 

Thank you! 

 

 

https://www.ncbi.nlm...pubmed/22961121

The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review.

Abstract

Due to the progressive aging of the population and to the age-associated increase in its incidence, Alzheimer's disease (AD) will become in near future one of the major challenges that healthcare systems will have to face with in developed countries. Since the pathophysiological process of AD is thought to begin many years before the clinical diagnosis of dementia, in theory there is an opportunity for preventive therapeutic interventions. In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, in the beneficial effects of some natural compounds in preventing various age-related pathologic conditions, including brain aging and neurodegeneration. Homotaurine, a small aminosulfonate compound that is present in different species of marine red algae, has been shown, in both in vitro and in vivo models, to provide a relevant neuroprotective effect by its specific anti- amyloid activity and by its γ-aminobutyric acid type A receptor affinity. The therapeutic efficacy of homotaurine in AD has been investigated in a pivotal Phase III clinical study that did not reach its pre-defined primary endpoints. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effects. In this review, we will examine the pre-clinical and clinical evidence supporting the potential role of homotaurine as a promising candidate for both primary and secondary prevention of AD.

 

Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain.

Hey JA, Kocis P, Hort J, Abushakra S, Power A, Vyhnálek M, Yu JY, Tolar M.

CNS Drugs. 2018 Sep;32(9):849-861. doi: 10.1007/s40263-018-0554-0.

PMID:30076539

 

Synergistic Inhibitory Effect of GQDs-Tramiprosate Covalent Binding on Amyloid Aggregation.

Liu Y, Xu LP, Wang Q, Yang B, Zhang X.

ACS Chem Neurosci. 2018 Apr 18;9(4):817-823. doi: 10.1021/acschemneuro.7b00439. Epub 2018 Jan 5.

PMID:29244487

 

Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer's Disease Suggest Disease Modification Potential.

Abushakra S, Porsteinsson A, Scheltens P, Sadowsky C, Vellas B, Cummings J, Gauthier S, Hey JA, Power A, Wang P, Shen L, Tolar M.

J Prev Alzheimers Dis. 2017;4(3):149-156. doi: 10.14283/jpad.2017.26.

PMID:29182706

 

 

 

 

[Turnbuckle]

 

Tried my first round,  15 mg of taurine way too much for me, groggy and dozing all next day.  Otherwise felt good.  My aged (69) nerves were tingly in a pleasant way.  

 

 

 

 

I'm assuming you meant 15 grams rather than 15 mg of taurine. If that is too much, cut it back to whatever works for you. Taurine has very low toxicity, stimulates neural stem cells, acts as an antioxidant against Aβ and contributes weakly to its dissolution in mice. It is also cheap and widely available. Homotaurine has been much less studied, is expensive and difficult to get. And as HEPPS is doing most of the work re Aβ dissolution, I don't see the value in changing out taurine. But do cut it back.

Edited by Turnbuckle, 24 September 2018 - 08:43 PM.

[Moumou]

I had five years ago a discution at the INSERM (French National Institute of Health and Medical Research) with a Specialist of PD, he told me they followed prions involved in PD going from the gut to the nose and brain through the autonomic nervous system.

 

https://www.scienced...969996116302947

 

> Fafner55, a Tau deficient mouse will have olfactory imperment ; https://actaneurocom...0478-018-0560-y

 

> Turnbuckle, maybe we need more investigation on olfactory as primary path for AD and PD proteins and maybe dissolving them more efficiently.

 

https://onlinelibrar....1002/mds.27250

 

https://www.nature.c...598-017-09481-x

 

 

There is  an affinity of taurine for olfactory bulb.

 

By region, taurine concentration is highest in the olfactory bulbs (an area of sustained neurogenesis), followed by the cerebellum and then cerebral cortex. By cell type, taurine concentration is highest in the cerebellar Purkinje cells, an established target exquisitely vulnerable to prenatal alcohol exposure. Taurine is the highest free AA in milk, further suggesting a role in neuronal maturation. Across species, taurine is critically implicated in brain development and in maintaining neuronal homeostasis by acting as a model osmoregulator and intracellular calcium modulator (El Idrissi and Trenkner, 2004, Pasantes-Morales and Hernández-Benítez, 2010). Taurine deficiency during development correlates with impaired neuronal migration, proliferation, and organization, yet the mechanisms of taurine requirements for nervous system maturation are not yet fully understood (Pasantes-Morales & Hernández-Benítez, 2010). Taurine disruption in the developing brain correlates with impaired sensory integration and cortical processing, yet not with somatic growth impairments (Sturman, 1993, Uauy et al., 2001). This phenotype is a hallmark for many children affected with FASDs, and our working hypothesis is that taurine is a key mechanistic component involved in neuropathology underlying behavioral deficits of FASD. (https://www.scienced...741832917307929)

 

 

Maybe we should make an Intranasal solution of - Hepps + Ascorbic Acid (+ Protollin?) - instead of Intranasal Insuline currently tested by Lostfalco (http://www.lostfalco...anasal-insulin/  (https://www.ncbi.nlm...pubmed/29392460)).

 

Include Piperine : Piperine increased striatal levels of GABA, glycine and taurine, and reversed pilocarpine-induced increases in nitrite contents in sera and brain. (https://www.scienced...091305713000063)

 

 

Edited by Moumou, 25 September 2018 - 01:07 AM.

[bladedmind]

 

 

 

 

I'm assuming you meant 15 grams rather than 15 mg of taurine. If that is too much, cut it back to whatever works for you. Taurine has very low toxicity, stimulates neural stem cells, acts as an antioxidant against Aβ and contributes weakly to its dissolution in mice. It is also cheap and widely available. Homotaurine has been much less studied, is expensive and difficult to get. And as HEPPS is doing most of the work re Aβ dissolution, I don't see the value in changing out taurine. But do cut it back.

 

 

Yes, I meant 15 g, not mg.  Doing 3g of taurine tonight and will increase until discomfort; also am phasing into HEPPS.  Thanks for your advice!  

[tolerant]

I have followed the latest incarnation of the protocol for the past two days. I do not feel any different. If I continue to feel that the protocol doesn't make a difference to my cognitive impairment, for how long should it be continued? And will continuing it with no change in cognition for that period of time mean that I do not have amyloid beta plaques and tau?

 

Alternatively, can I use the substances from the protocol differently to establish whether I have amyloid beta plaques and tau in a shorter period of time? For example, use a high dose of HEPPS with no oleuropein and see whether it increases my cognitive impairment, and if it doesn't, conclude that I do not have amyloid beta plaques and following the protocol will not result in improvement in cognition. Similarly with tau, can I use the "dissolve" portion of the protocol without nicotinamide for diagnostic purposes? If so, which substances in the latest protocol constitute the "dissolve" part in relation to tau? Initially, it was methylene blue, but it's not clear to me which substance or substances have replaced methylene blue in the latest protocol.

[Turnbuckle]

I have followed the latest incarnation of the protocol for the past two days. I do not feel any different. If I continue to feel that the protocol doesn't make a difference to my cognitive impairment, for how long should it be continued? And will continuing it with no change in cognition for that period of time mean that I do not have amyloid beta plaques and tau?

 

 

Patience, tolerant. Try it for two weeks. As for your other questions, answer these: Are you past sixty? Do you have at least one APOE4 gene? If no to both and you don't feel anything after a couple of weeks, then maybe it is something else. Though I expect everyone of a certain age has some Aβ, even if asymptomatic. You can actually have quite a bit--

 

Postmortem studies, previously the only method of examining Aβ, have found that 25–30% of individuals with no clinical symptoms of dementia have levels of Aβ equal to the diagnostic level for AD 

https://www.ncbi.nlm...les/PMC2844114/

 

 

The global incidence of APOE4 is about 14%, which means that roughly half of those with high levels of Aβ don't carry the allele.

 

As for tau, several ingredients impact tau, including nicotinamide, which acts against hyperphosphorylation, and those derived from olive oil--

 

We report herein the ability of three natural phenolic derivatives obtained from olives and derived food products to prevent such Tau fibrillization in vitro, namely hydroxytyrosol, oleuropein, and oleuropein aglycone. The latter was found to be more active than the reference Tau aggregation inhibitor methylene blue on both wild-type and P301L Tau proteins, inhibiting fibrillization at low micromolar concentrations. 

https://www.ncbi.nlm...pubmed/21333710

 

 

I stopped using MB as its use is so problematical, staining anything it touches.

 

ALCAR is another supplement that goes after tau, and might make a good addition--

 

ALCAR (50 mg/d . rat, per os) for two weeks efficiently improved the OA-induced spatial memory retention impairment of the rats. ALCAR antagonized tau hyperphosphorylation at multiple AD sites and it abated the OA-induced PP2A inhibition and oxidative stress. Our study provides the first in vivo evidence that ALCAR can attenuate AD-like PP2A inhibition, tau hyperphosphorylation, and spatial memory deficit of the rats. It suggests that ALCAR may hold potential in AD treatment.

https://www.ncbi.nlm...pubmed/20110616

 

 

The damage wrought in AD proliferates glial cells and those themselves can cause symptoms. It may take longer for that to be reversed by natural processes. While I'm not aware of any treatments to reverse that faster, removing the stimulus (plaques) should reverse the response (glial cells).

Edited by Turnbuckle, 25 September 2018 - 11:00 AM.

[tolerant]

Patience, tolerant. Try it for two weeks. As for your other questions, answer these: Are you past sixty? Do you have at least one APOE4 gene? If no to both and you don't feel anything after a couple of weeks, then maybe it is something else. Though I expect everyone of a certain age has some Aβ, even if asymptomatic. You can actually have quite a bit--

 

Thanks for responding. So you don't think that trying, say, 4 g of HEPPS by itself and seeing what response it elicits is a good idea? I must admit that I have been taking all the substances in the protocol before bed, so perhaps their half-lives are not long enough for me to have experienced the initial deterioration in cognitive functioning that has been mentioned in this thread.

 

I am only 38. I don't know if I have APOE4 genes. How can I do a test for that? Is it a blood test that you can request from your doctor or do you go to one of those websites like 23andme? This is very much new territory for me.

 

Also, today I read the ion channel hypothesis of AD: https://en.wikipedia...eimer's_disease. I don't want to derail the thread, but can I ask a quick question? The way I read this theory is that amyloid beta increases calcium influx into neurons. I have had severe major depression and anxiety for the last six-and-a-half years and have been experiencing cognitive decline for the past 14 months. One of only two medications that significantly alleviated my symptoms for a short period (before tolerance developed) was pregabalin. Pregabalin inhibits influx of calcium into neurons: https://www.ncbi.nlm.nih.gov/pubmed/11804619

 

Could it be that asymptomatic (as far as AD is concerned) amyloid beta caused disruption of calcium ion homeostasis, which in turn caused depression and anxiety and five-and-a-half years later became symptomatic causing cognitive impairment?

Edited by tolerant, 25 September 2018 - 11:50 AM.

[Turnbuckle]

Thanks for responding. So you don't think that trying, say, 4 g of HEPPS by itself and seeing what response it elicits is a good idea? I must admit that I have been taking all the substances in the protocol before bed, so perhaps their half-lives are not long enough for me to have experienced the initial deterioration in cognitive functioning that has been mentioned in this thread.

 

Not everyone experiences that.

 

I am only 38. I don't know if I have APOE4 genes. How can I do a test for that? Is it a blood test that you can request from your doctor or do you go to one of those websites like 23andme? This is very much new territory for me.

 

 

Early onset (at 40-50 years) is rare -- one in twenty. If you have it then very likely you have family members who have it. And APOE4 is not the only gene involved, just the most common. There are several genetic testing companies that are rather cheap. You can use 23andme and pay the additional hundred dollars for their health report, or upload their data to promethease for a few dollars. 

 

Also, today I read the ion channel hypothesis of AD: https://en.wikipedia...eimer's_disease. I don't want to derail the thread, but can I ask a quick question? The way I read this theory is that amyloid beta increases calcium influx into neurons. I have had severe major depression and anxiety for the last six-and-a-half years and have been experiencing cognitive decline for the past 14 months. One of only two medications that significantly alleviated my symptoms for a short period (before tolerance developed) was pregabalin. Pregabalin inhibits influx of calcium into neurons: https://www.ncbi.nlm...ubmed/11804619

 

 

 

More than likely your symptoms are coming from your medications and not from AD. You can find people complaining about mental decline after taking Lyrica.

Edited by Turnbuckle, 25 September 2018 - 12:38 PM.

[tolerant]

Not everyone experiences that.

 

Yes, I understand. So even if I have amyloid beta, I'm guaranteed to experience the initial deterioration. But trying to force it may be a good exercise, because if I do experience it, I can be pretty much certain that I need to continue following the protocol.

 

 

Early onset (at 40-50 years) is rare -- one in twenty. If you have it then very likely you have family members who have it.

 

I assume you mean family members who have early onset AD. I have a 92-year-old grandfather with dementia, who first started showing symptoms when he was about 85, but that doesn't count, right?

 

 

And APOE4 is not the only gene involved, just the most common. There are several genetic testing companies that are rather cheap. You can use 23andme and pay the additional hundred dollars for their health report, or upload their data to promethease for a few dollars.

 

Thanks for the info. I might do that.

 

 

More than likely your symptoms are coming from your medications and not from AD. You can find people complaining about mental decline after taking Lyrica.

 

That's what the doctors said. Except they see clonazepam as the chief suspect. The problem with that is that I had been on these medications for years prior to my cognitive decline starting. When I last looked, there was some literature on clonazepam caused mild cognitive impairment, but not a full-scale decline that permeates every minute and every aspect of my life, which is what I have. I have not seen any literature on Lyrica doing that. I might investigate further. Add to that that in the last six months I have cut my clonazepam dose in half, during which period my cognitive symptoms continued to worsen, and the theory doesn't stack up. I myself tend to favour the diagnosis of pseudodementia, once every form of dementia is ruled out.

Edited by tolerant, 26 September 2018 - 12:06 AM.

[Moumou]

o Tolfenamic Acid (an NSAID) Reduces Amyloid Beta Protein Levels :


"Results show that tolfenamic acid generated a much greater decline in the levels of the more aggregative Amyloid Beta form, Amyloid Beta (1-42), whose levels were significantly lower than controls  by  the  following  percentages:  33%  with  1  mg/kg,  68% with 5 mg/kg, 33% with 25 mg/kg, and 29% with 50 mg/kg Fig. (5B); p<0.05"

"Mass  spectra  data  provide  evidence  that  tolfenamic  acid was able to cross the blood brain barrier and was available in the  brain  after  oral  dosing."

 

https://www.ingentac...000008/art00005

 

---

o Clearance of Amyloid Beta and Tau in Alzheimer’s Disease: from Mechanisms to Therapy

"The expression of APOE ε4 allele is related to the reduction of Aβ clearance from the brain by impairing its arterial perivascular drainage, accompanied by changes of protein levels in cerebrovascular basement membrane (Hawkes et al.2012). Immune complexes can deposit in the basement membranes of cerebral artery walls, impeding perivascular drainage of Aβ (Carare et al.2013). It has also been discovered that a long time high-fat diet also impairs perivascular drainage of Aβ across the cerebrovascular basement membrane (Hawkes et al.2015). In addition, Aβ deposition in the vascular wall gives rise to CAA, and CAA in turn can impair perivascular solute drainage from the brain (Hawkes et al.2014)."

"A study suggested that Aβ is removed from CSF to cervical lymph nodes via perineural space of the olfactory nerve (Picken 2001  ; Pollay 2010)

"In addition, a recent experiment showed that a great deal of Aβ in the blood circulation may combine with serum albumin (Stanyon and Viles 2012 ), which provided a novel clearance pathway in periphery."

https://link.springe...2640-018-9895-1

---

& More infos on the Olfactory route.

     
o A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb

*Aberrant cell cycle re-entry (CCE)

"Adult born neurons in the olfactory bulb (OB) can re-enter the cell cycle (CCE; light green box) following various cellular events (highlighted in yellow boxes). These include DNA damage or aberrant cell cycle control due to loss of function mutations in key cell cycle genes such as Rb, p130, p53, Pten or others. CCE (G1/S phase checkpoint) requires phosphorylation of Rb by Cdk4/Cyclin D1 among others mitogenic events. CCE primarily triggers DNA repair (dark green box) but may be possibly accompanied by inflammatory response of resident microglia and/or non-mitogenic signaling such as neuroplasticity. Neurons with failed DNA repair may proceed to the S-phase and undergo: (1) apoptosis e.g., mediated by E2F1, (2) senescence induced by p53 or p16 (with manifestation of senescence-associated secretory phenotype (SASP) (red boxes) or (3) a mitotic-steady state with accumulation of additional insults that will lead to protein aggregation(s)/pathology (yellow boxes) and neurodegeneration eventually (red box). The early steps of prion-like pathologies e.g., Tau phosphorylation may be triggered by several potential kinases with upregulated activities such as cytoplasmic Cdk5, GSK3β, c-Abl and/or others."

"Then again, another perspective proposes a “two hit hypothesis” in AD, whereby a first hit of mitogenic signaling dysregulation induces CCE causing a “mitotic steady state” that is not sufficient to cause cell death. However, this comes at the expense of accumulating more insults whereby a second hit such as of oxidative stress then triggers neuronal degeneration (Zhu et al., 2007; Aliev et al., 2014; Khan et al., 2016). Both events are necessary and sufficient to cause the disease and may be common to other neurodegenerative diseases (Figure 3). Indeed, using three different mouse models of AD, Yang et al. demonstrated that cortical neurons undergo DNA replication 6 months before developing β-amyloid plaques (known to accumulate in AD patients) or displaying activated microglia, yet without committing to cell death"

"It is noteworthy to mention that while CCE in the young adult OB may be directly linked to a neurodegenerative role, the aged OB is more adjusted to reduce neuronal loss which can reflect different roles of cell-cycle regulators during aging (Ohsawa et al., 2009). Finally, proteomic analysis of human postmortem OBs detected a specific deregulation of the DNA damage pathway in initial AD stages and that of the cell cycle in intermediate AD stages, albeit with high heterogeneity within the same AD stage (Zelaya et al., 2015)."

"Interestingly, the olfactory system offers alternative mechanisms of delivery by the very means of which it is most vulnerable to environmental toxic factors, that is its direct exposure to the nasal cavity (Doty, 2008). In line with this, Kovács T reviews intranasal delivery of insulin and cholinesterase inhibitors as a promising therapeutic pathway to treat or delay AD pathology (Kovács, 2013). While more research is warranted, the olfactory system serves as a gateway for disease initiation and progression, while also an early and accessible window for therapeutic intervention."

https://www.frontier...2018.00144/full

---

 

o Injected Amyloid Beta in the Olfactory Bulb Transfers to Other Brain Regions via Neural Connections in Mice


"The study has shown that injected human Amyloid β (1-42) is taken up by neurons in the different layers of OB and can be rapidly transferred to interconnected brain regions via neural connections. In the main olfactory system, OB mitral cells project axons to multiple brain regions including ipsilateral AON, olfactory tubercle (OT), TT, PC, Am, and EC. HuAβ positive cells were found in nearly all these brain regions, suggesting that injected Aβ 1–42 could be transferred by anterograde transport from the OB to the connected structures. However, no huAβ positive cells were found in OT which receives direct axonal projection from the OB. It is a surprising phenomenon. HuAβ might be cleared quickly in OT or be taken up inefficiently by neurons in OT. However, the exact reason why OT lacks Aβ positive staining remains to be further investigated. Injected Aβ 1–42 could also be transferred by retrograde transport from the OB to the connected brain areas since nearly all the brain regions which send axonal projections to the OB such as ipsilateral and contralateral AON and FC and ipsilateral TT and PC were found to contain Aβ positive cells."

"In summary, we have demonstrated for the first time that huAβ injected into the OB can be taken up by neurons in the OB and transported into connected brain structures, triggering neuronal apoptosis. The results supported the OB olfactory hypothesis of AD pathology."

 

https://link.springe...2035-017-0446-1

---

 

"Hyperphosphorylation of tau is a major pathological change in AD and is critical in the formation of neurofibrillary tangles, and tau proteins have been found to be abnormally deposited in the dystrophic olfactory epithelium of AD patients. The increased p-tau/t-tau ratio in the nasal cavity could be the result of pathologic changes in the olfactory epithelium in AD."

"Ayala-Grosso et al. reported that patient-derived olfactory stromal cells from biopsies of olfactory mucosa expressed Aβ peptides. Our previous study using a rat model showed that Aβ peptides injected in the brain were transported from the brain into the nasal cavity. The present study showed that the p-tau/t-tau ratio in the nasal cavity was significantly higher in AD cases than in controls, in the olfactory cleft and middle nasal meatus. Interestingly, the olfactory cleft and middle nasal meatus are deeper in the nasal cavity where the biomarker levels are closer to those of the olfactory epithelium and cranial cavity."

https://content.iosp...2#ref014 ref015

Edited by Moumou, 26 September 2018 - 12:39 AM.

[Empiricus]

I've carried out my version of the protocol for about 10 days over past 3 weeks.  Four days of HEPPS at 350 mg, increasing to 600 mg for 2 days, and then 1000 mg for 2 days. I would consume about 2-4 tablespoons of fresh olive oil, rest of the protocol similar to Turnbuckle's, except I added a number of other things from the studies.  My reaction to 1 drop of M Blue wasn't pleasant, so I reduced dosage to 1/4 drop per day for 4 days.  Results have been mixed.  I can't decide if the symptoms (mainly typos in writing) are worse or better. You can tell it's doing something, because you can literally feel some unusual sensations.  My suspicion is that getting sufficient olive phenols may be essential for this to work, and I may not be getting a sufficient amount relative to the above doses of HEPPS. 

 

Over the past 2 days I have reduced the HEPPS to about 200 mg, and added about 50 mg of olive leaf extract to the olive oil.  I'm keeping the taurine dose high and dropping the TUDCA for awhile.   

 

FWIW, here are some things I have added to my protocol, with references:

 

Lycopene (300 mg)

Lycopene attenuates Aβ1–42 secretion and its toxicity in human cell and Caenorhabditis elegans models of Alzheimer disease  https://www.scienced...304394015301725

Implicating the role of lycopene in restoration of mitochondrial enzymes and BDNF levels in β-amyloid induced Alzheimer׳s disease. https://www.ncbi.nlm...pubmed/25066110

Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons. https://www.ncbi.nlm...pubmed/26816095

 

Fisetin (200 mg)

Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.  https://www.ncbi.nlm...pubmed/26944285

 

Epigallocatechin 3-Gallate (3-5 cups green tea)

Epigallocatechin 3-Gallate as an Inhibitor of Tau Phosphorylation and Aggregation: A Molecular and Structural Insight. https://www.ncbi.nlm...pubmed/29181486

EGCG inhibits the oligomerization of amyloid beta (16-22) hexamer: Theoretical studies.  https://www.ncbi.nlm...pubmed/28658644

"the binding free energy of the EGCG to the Aβ peptides is slightly larger than that of the curcumin…"

 

Blueberry leaf  (500 mg)

Blueberry (Vaccinium virgatum) leaf extracts protect against Aβ-induced cytotoxicity and cognitive impairment.  https://www.ncbi.nlm...pubmed/24117094

 

Black Cumin (1 gram of oil)

Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity. https://www.ncbi.nlm...pubmed/23537659  

 

Rutin (2 grams)

Troxerutin protects hippocampal neurons against amyloid beta-induced oxidative stress and apoptosis https://www.ncbi.nlm...pubmed/29285004

Note: Troxerutin is a flavonol, a type of flavonoid, derived from rutin.

 

Folic Acid + A Tocopherol (1000 mcg Folic + 1 Jarrow toco capsule)

Folic acid plus α-tocopherol mitigates amyloid-β-induced neurotoxicity through modulation of mitochondrial complexes activity. https://www.ncbi.nlm...pubmed/21157027

"Oral treatment with folic acid (50 mg/kg) plus α-tocopherol (500 mg/kg), once a day during 14 consecutive days, protected mice against the Aβ₁₋₄₀-induced cognitive decline, synaptic loss, and neuronal death."

 

Turnbuckle's protocol utilizes olive phenols to promote clearance.  For some people at least, the impairments may result from defects in the clearance mechanisms.  See: Clearance of beta-amyloid in the brain https://www.ncbi.nlm...pubmed/25312211

 

Some additional things that may assist with clearance: 

 

Caffeine (2 cups coffee)

Enhanced brain amyloid-β clearance by rifampicin and caffeine as a possible protective mechanism against Alzheimer's disease https://www.ncbi.nlm...bmed/22504320. 

 

D3 and curcumin (sunlight + longvida curcumin)  

1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients  https://www.ncbi.nlm...pubmed/19433889

 

Vigorous exercise (1 hour treadmill) 

A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer's disease. https://www.ncbi.nlm...pubmed/26563933

"Soluble Aβ42 levels also decreased significantly in an exercise training dose-dependent manner  in both the cortex and hippocampus. Five proteins involved in Aβ clearance ...were elevated by exercise training with its intensity playing a role in each case."

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels.  https://www.ncbi.nlm...pubmed/29948724

"In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD."

 

Omega 3 (1 capsule) 

Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system https://www.ncbi.nlm...pubmed/27789520

 

Selenium-enriched yeast (2 tablets)

Selenium-enriched yeast inhibited β-amyloid production and modulated autophagy in a triple transgenic mouse model of Alzheimer's disease https://www.ncbi.nlm...pubmed/30043821

 

jujuboside (1/2 cup dried jujuba fruits)

Jujuboside A promotes Aβ clearance and ameliorates cognitive deficiency in Alzheimer's disease through activating Axl/HSP90/PPARγ pathway https://www.ncbi.nlm...pubmed/30128052

"JuA significantly reduced the soluble Aβ42 levels and plaque numbers in the brain."

 

Edited by Empiricus, 26 September 2018 - 05:38 AM.

[tolerant]

So far, the people in this thread who have benefited from Turnbuckle's protocol are Turnbuckle himself and resveratrol_guy. And both recovered certain aspects of cognition which were impaired prior to using the protocol. Which is, interestingly, not in line with what the author behind the studies of EPPS effect on amyloid beta plaques said, namely:

 

"I do not believe EPPS or other amyloid clearing drug candidates will make Alzheimer patients recover their damaged brains. However, I strongly believe these drug candidates will halt the neurodegeneration and rescue patients from death."

 

I almost want to have AD, because I assume other forms of dementia are untreatable. Today I was upset to discover that there's alcohol-related dementia, for which I would probably meet the loose diagnostic criteria.

 

Empiricus, why do you consume olive oil? Is that instead of oleuropein and hydroxytyrosol? Or in addition? You list so many additional substances. My cognition is already stretched by Turnbuckle's protocol, so I probably won't be taking any additional ones, unless I show some improvement first.

 

And do you think there is any way to use these substances to "force" a diagnosis of AD or absence thereof? What was the adverse reaction to MB that you experienced? And what do we make of Turnbuckle's experience with a high dose of MB, where he first experienced unusual mental clarity, but then found that he couldn't follow the plot of a television program? Why did taking the MB with niacinamide (which should, in theory, both dissolve and clear the tau tangles) not result in the regaining og that unusual mental clarity but only in a return to baseline?

Edited by tolerant, 26 September 2018 - 07:20 AM.

[Empiricus]

Olive oil contains most of the same phenols as olive leaf, only less concentrated, and it's easier tolerated and proven suitable for daily consumption. If you research olive leaf, a popular herbal remedy, you'll see it makes some people feel ill. This side-effect is popularly attributed to something called the "Herxheimer's reaction." However, I have found no studies lending support to this hypothesis.  On the other hand, one study suggests olive leaf may be toxic to the kidneys and liver:

 

Toxicity of Olive Leaves (Olea europaea L.) In Wistar Albino Rats

https://scialert.net....2012.1175.1182

"Feeding olive leaves extracts to Wistar albino rats for 6 weeks at a dose up to 0.9% resulted in hepatocellular and renal abnormalities."

 

The good news is that, according to one study, olive oil also shows promise for our purposes.  So it might not be necessary to consume any olive leaf extracts to obtain the necessary phenols.  So far, I have stayed away from olive leaf extract, as it gives me nausea and body aches.  Instead I have been consuming a lot of fresh olive oil. However, I'm starting to gain weight, so as an experiment, I'm replacing some of the olive oil with a tiny amount of a leaf extract.  

 

Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice. https://www.ncbi.nlm...ubmed/26344778 

"...beginning at an age after Aβ accumulation starts, showed improved clearance across the blood-brain barrier and significant reduction in Aβ levels....  Collectively, results of this study suggest that the long-term consumption of EVOO-containing diet starting at early age provides a protective effect against AD and its related disorder CAA."

 

Edited by Empiricus, 26 September 2018 - 07:11 AM.

[tolerant]

Fair enough, Empiricus. I'm following Turnbuckle's protocol to the letter, including the two olive leaf substances and don't feel physically ill. Have a look, if you can, at my previous post. I added a paragraph on MB.

Edited by tolerant, 26 September 2018 - 07:52 AM.

[Andey]

---

 

  Your condition similar to what people describe while having some brain inflammation.

 Look at Joe Rogan`s podcast with Dr. Mark Gordon if interested. In this case, it's from TBI but inflammation could have different causes. 

 I've kinda experienced it too when treated Lyme.

 Good thing is that decline in cognitive ability is reversible (at least for the most part).