1230 replies to this topic

[MikeDC]

https://www.ncbi.nlm...oside alzheimer

Nicotinamide Riboside is the best to prevent and reverse Alzheimer's disease. People who take Niagen early in life will not get Alzheimer's. Not sure how far Niagen can reverse the disease. My father who is 85 years old and has a full blown Alzheimer's has seen improvement after 4 months of 250 mg Niagen. Higher dose is recommended though.

[mag1]

Substantial amount of excitement in the dementosphere about:

 

http://journals.plos...al.pmed.1002258

 

Interested in when you will experience dementia?

[ta5]

PLoS One. 2017 Apr 14;12(4):e0175369.
Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer's disease: Alleviation by pantethine.

van Gijsel-Bonnello M1, Baranger K1, Benech P1, Rivera S1, Khrestchatisky M1, de Reggi M1, Gharib B1.

Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD) and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter) to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells. Tg astrocytes displayed also a prominent basal inflammatory status, with accentuated reactivity and increased expression of the inflammatory cytokine interleukin-1 beta (IL-1β). Compensatory mechanisms were activated in Tg astrocytes, including: i) the hexose monophosphate shunt with the consequent production of reducing species; ii) the induction of hypoxia inducible factor-1 alpha (HIF-1α), known to protect against amyloid-β (Aβ) toxicity. Such events were associated with the expression by Tg astrocytes of human isoforms of both amyloid precursor protein (APP) and presenilin-1 (PS1). Similar metabolic and inflammatory changes were induced in WT astrocytes by exogenous Aβ peptide. Pantethine, the vitamin B5 precursor, known to be neuroprotective and anti-inflammatory, alleviated the pathological pattern in Tg astrocytes as well as WT astrocytes treated with Aß. In conclusion, our data enlighten the dual pathogenic/protective role of astrocytes in AD pathology and the potential protective role of pantethine.

PMID: 28410378

[davis89x]

Scientists hope they have found a drug to stop all neurodegenerative brain diseases, including dementia.

 

In 2013, a UK Medical Research Council team stopped brain cells dying in an animal for the first time, creating headline news around the world.

But the compound used was unsuitable for people, as it caused organ damage.

Now two drugs have been found that should have the same protective effect on the brain and are already safely used in people.

[...]

Prof Mallucci told the BBC News website: "Both were very highly protective and prevented memory deficits, paralysis and dysfunction of brain cells."

The best known drug of the pair is trazodone, which is already taken by patients with depression.

The other, DBM, is being tested in cancer patients.

[source]

[TRUGAN]

Scientists hope they have found a drug to stop all neurodegenerative brain diseases, including dementia.

 

In 2013, a UK Medical Research Council team stopped brain cells dying in an animal for the first time, creating headline news around the world.

But the compound used was unsuitable for people, as it caused organ damage.

Now two drugs have been found that should have the same protective effect on the brain and are already safely used in people.

[...]

Prof Mallucci told the BBC News website: "Both were very highly protective and prevented memory deficits, paralysis and dysfunction of brain cells."

The best known drug of the pair is trazodone, which is already taken by patients with depression.

The other, DBM, is being tested in cancer patients.

[source]

 

 

looks like trazodone is easy to get online and cheap. Assuming you trust the source.

[MikeDC]

Scientists hope they have found a drug to stop all neurodegenerative brain diseases, including dementia.

In 2013, a UK Medical Research Council team stopped brain cells dying in an animal for the first time, creating headline news around the world.
But the compound used was unsuitable for people, as it caused organ damage.
Now two drugs have been found that should have the same protective effect on the brain and are already safely used in people.
[...]
Prof Mallucci told the BBC News website: "Both were very highly protective and prevented memory deficits, paralysis and dysfunction of brain cells."
The best known drug of the pair is trazodone, which is already taken by patients with depression.
The other, DBM, is being tested in cancer patients.

[source]

looks like trazodone is easy to get online and cheap. Assuming you trust the source.

The professor is nuts. There is no evidence that trazodone prevents or cures neuradegenerative diseases.

[TRUGAN]

I dont think he expects it to be a cure. He wants to do clinical trials to see if it slows down the progression in humans. It may be like everything else and only work in the mice and not us big rats. Now, I dont know anything about this guy or is credibility but here is the source article.

 

https://academic.oup...eIF2-P-mediated

 

[Logic]

I or my rat have no reason to use it so it will go in the deep freeze if I am successful at making it.

I think you will be as the process is pretty much foolproof.
 

Next, I will look at making other useful phages that might be good for general health. So far all I have seen on the market is the product floraphage but I'm not convinced it's all that beneficial.

In fact I think anyone watching the video you posted  and taking head of what the selective elimination of bad bacteria, including senescent cell preservation, can do, is ahead of the game.

This is especially true in the gut with its cell turnover of 5 days = short telomeres.
The systemic effect of reducing NF-kB on telomerase, cell signalling, replacement by stem cells etc, NAD+, SIRT etc upregulation due to CD38 reduction, etc-etc is potentially unparalleled IMHO.  (Gut feeling  )

I for one would gladly visit you and donate bacteria for bacteriophages 'research' specific to the the bacteria I want dead.
The question is; how to isolate said bad bacteria?

Edited by Logic, 22 April 2017 - 01:52 AM.

[tunt01]

 

The professor is nuts. There is no evidence that trazodone prevents or cures neuradegenerative diseases.

 

 

Even the paper says the mice are still loaded with prions or misfolded proteins.  It's not actually clearing misfolded proteins.  Trazodone won't be much more than symptomatic relief or at best be a very downstream intervention.

[ceridwen]

It never claimed to be a cure but did claim to prevent further damage and that would be wonderful

[TRUGAN]

 

I or my rat have no reason to use it so it will go in the deep freeze if I am successful at making it.

I think you will be as the process is pretty much foolproof.
 

Next, I will look at making other useful phages that might be good for general health. So far all I have seen on the market is the product floraphage but I'm not convinced it's all that beneficial.

In fact I think anyone watching the video you posted  and taking head of what the selective elimination of bad bacteria, including senescent cell preservation, can do, is ahead of the game.

This is especially true in the gut with its cell turnover of 5 days = short telomeres.
The systemic effect of reducing NF-kB on telomerase, cell signalling, replacement by stem cells etc, NAD+, SIRT etc upregulation due to CD38 reduction, etc-etc is potentially unparalleled IMHO.  (Gut feeling  )

I for one would gladly visit you and donate bacteria for bacteriophages 'research' specific to the the bacteria I want dead.
The question is; how to isolate said bad bacteria?

 

 

 

 

Turns out the price the lab gave me was better than I thought. I only asked for a small amount so thats what he quoted me. Later I found out that I could have the entire batch for that price which is several ml but noone seemed interested so I let it go. If we ever had 10 or so people interested it would actually be affordable and safer.

[Logic]

 

 

I or my rat have no reason to use it so it will go in the deep freeze if I am successful at making it.

I think you will be as the process is pretty much foolproof.
 

Next, I will look at making other useful phages that might be good for general health. So far all I have seen on the market is the product floraphage but I'm not convinced it's all that beneficial.

In fact I think anyone watching the video you posted  and taking head of what the selective elimination of bad bacteria, including senescent cell preservation, can do, is ahead of the game.

This is especially true in the gut with its cell turnover of 5 days = short telomeres.
The systemic effect of reducing NF-kB on telomerase, cell signalling, replacement by stem cells etc, NAD+, SIRT etc upregulation due to CD38 reduction, etc-etc is potentially unparalleled IMHO.  (Gut feeling  )

I for one would gladly visit you and donate bacteria for bacteriophages 'research' specific to the the bacteria I want dead.
The question is; how to isolate said bad bacteria?

 

 

 

 

Turns out the price the lab gave me was better than I thought. I only asked for a small amount so thats what he quoted me. Later I found out that I could have the entire batch for that price which is several ml but noone seemed interested so I let it go. If we ever had 10 or so people interested it would actually be affordable and safer.

 

 

Do you mean for M13 specifically?
It was you who posted the video on home bacteriophage isolation wasn't it?
I want to kill off many different bacteria!  

[ceridwen]

I'd be willing to try it

[MikeDC]

I'd be willing to try it

If you are willing to try, the most likely drug that can prevent and cure Alzheimer's is Niagen. A trial will start soon. My father has improved after 4 months of Niagen.

[Der Springende Punkt]

 

I'd be willing to try it

If you are willing to try, the most likely drug that can prevent and cure Alzheimer's is Niagen. A trial will start soon. My father has improved after 4 months of Niagen.

 

 

Are you referring to this study?: https://clinicaltria...how/NCT02942888

May I ask what dosage your father take?

[ta5]

These studies are not primarily focused on Alzheimer's. They are on hearing loss and traumatic brain injury, though they talk a little about how it relates to Alzheimer's and dementia. This first one below is from a few days ago, the next one is from 2016, and it references another study from 2013, all by the same authors.

 

Free Radic Biol Med. 2017 Apr 21. pii: S0891-5849(17)30546-4.

Antioxidants Reduce Neurodegeneration and Accumulation of Pathologic Tau Proteins in the Auditory System after Blast Exposure.

Du X1, West MB1, Cai Q1, Cheng W1, Ewert DL1, Li W1, Floyd RA2, Kopke RD3.

Cochlear neurodegeneration commonly accompanies hair cell loss resulting from aging, ototoxicity, or exposures to intense noise or blast overpressures. However, the precise pathophysiological mechanisms that drive this degenerative response have not been fully elucidated. Our laboratory previously demonstrated that non-transgenic rats exposed to blast overpressures exhibited marked somatic accumulation of neurotoxic variants of the microtubule-associated protein, Tau, in the hippocampus. In the present study, we extended these analyses to examine neurodegeneration and pathologic Tau accumulation in the auditory system in response to blast exposure and evaluated the potential therapeutic efficacy of antioxidants on short-circuiting this pathological process. Blast injury induced ribbon synapse loss and retrograde neurodegeneration in the cochlea in untreated animals. An accompanying perikaryal accumulation of neurofilament light chain and pathologic Tau oligomers were observed in neurons from both the peripheral and central auditory system, spanning from the spiral ganglion to the auditory cortex. Due to its coincident accumulation pattern and well-documented neurotoxicity, our results suggest that the accumulation of pathologic Tau oligomers may actively contribute to blast-induced cochlear neurodegeneration. Therapeutic intervention with a combinatorial regimen of 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) significantly reduced both pathologic Tau accumulation and indications of ongoing neurodegeneration in the cochlea and the auditory cortex. These results demonstrate that a combination of HPN-07 and NAC administrated shortly after a blast exposure can serve as a potential therapeutic strategy for preserving auditory function among military personnel or civilians with blast-induced traumatic brain injuries.

PMID: 28438658

 

Oxid Med Cell Longev. 2016;2016:4159357.

Ameliorative Effects of Antioxidants on the Hippocampal Accumulation of Pathologic Tau in a Rat Model of Blast-Induced Traumatic Brain Injury.

Du X1, West MB1, Cheng W1, Ewert DL1, Li W1, Saunders D2, Towner RA2, Floyd RA2, Kopke RD3.

Traumatic brain injury (TBI) can lead to early onset dementia and other related neurodegenerative diseases. We previously demonstrated that damage to the central auditory pathway resulting from blast-induced TBI (bTBI) could be significantly attenuated by a combinatorial antioxidant treatment regimen. In the current study, we examined the localization patterns of normal Tau and the potential blast-induced accumulation of neurotoxic variants of this microtubule-associated protein that are believed to potentiate the neurodegenerative effects associated with synaptic dysfunction in the hippocampus following three successive blast overpressure exposures in nontransgenic rats. We observed a marked increase in the number of both hyperphosphorylated and oligomeric Tau-positive hilar mossy cells and somatic accumulation of endogenous Tau in oligodendrocytes in the hippocampus. Remarkably, a combinatorial regimen of 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) resulted in striking reductions in the numbers of both mossy cells and oligodendrocytes positively labeled for these pathological Tau immunoreactivity patterns in response to bTBI. This treatment strategy represents a promising therapeutic approach for simultaneously reducing or eliminating both primary auditory injury and nonauditory changes associated with bTBI-induced hippocampal neurodegeneration.

PMID: 27034735

 

Like CTE, the ongoing neurodegeneration associated with bTBIs has been shown to be a Tau protein-linked disorder, or tauopathy [10, 11]. In uninjured brains, the soluble microtubule-associated protein, Tau, is enriched in neuronal axons where it plays a key role in stimulating microtubule formation, outgrowth, and subsequent maintenance of cytoskeletal stability, thus promoting axonal and dendritic transport [12]. However, Tau is susceptible to stress-induced hyperphosphorylation in response to single or repetitive neurotraumas. Hyperphosphorylated Tau is prone to misfolding and aggregation, leading to destabilization of microtubules and, thus, compromised neuronal viability and function. Moreover, once initiated, stress-induced destabilization of Tau can result in propagative waves of Tau dysfunction, as hyperphosphorylated Tau inclusions have a propensity to recruit and subvert functional Tau proteins in a prion-like manner that can progress in a transcellular fashion [13, 14]. Although the neurofibrillary tangles (NFTs) that result from this pathophysiological process have long been appreciated as a central feature of neuropathies, such as Alzheimer's disease and dementia, it is now recognized that the oligomeric “seeds” of hyperphosphorylated Tau that initiate the formation of NFTs are sufficient for the neuronal cell death and cognitive deficits associated with these disorders [15]. Thus, early intervention strategies aimed at attenuating or eliminating the etiological precursors of NFTs would have significant clinical impact on both the acute and chronic manifestations of bTBI-related cognitive dysfunction.

 

HPN-07 is a new name for NXY-059, OKN-007, or Cerovive. These are all different names for Disufenton Sodium which is the disulfonyl derivative of the spin trap PBN (possibly to avoid patent issues from using plain PBN). PBN is broken down to produce NtBHA.

[MikeDC]

https://www.ncbi.nlm...r's disease nmn

https://www.ncbi.nlm...r's disease nmn

[rwac]

An Australian biotech company is launching a novel attack on Alzheimer's disease. Rather than following the traditional treatment paths, it is taking a new route.
This month the first of 174 patients on an international trial will begin taking a drug to lessen the level of the stress hormone, cortisol, in the brain.
There is evidence to suggest this hormone has role in Alzheimer's. It is not promoted as the sole cause of the disease but rather as a contributing factor.
Current wisdom holds that it is likely that a few factors combine to bring about Alzheimer's. Some think cortisol may be one of them.

...

The trial aims to use Xanamem, to lower cortisol in the brains of people with early mild Alzheimer's and assess whether this can delay further deterioration.

Read more: http://www.afr.com/l...20170506-gvzk57

[albedo]

Good find Rwac. I am only half surprised, it is not the first time cortisol is involved in brain disease, e.g. epilepsy: "...The unbalancing in morning cortisol and DHEAS levels was emphasized by increased C/Dr. Similar changes are present in aging and characterize other neurologic conditions (i.e., primary depression and dementia) (27–30)..."

Galimberti CA, Magri F, Copello F, et al. Seizure frequency and cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in women with epilepsy receiving antiepileptic drug treatment. Epilepsia. 2005;46(4):517-23. If the ratio cortisol/dhea-s turns to be also a possible drug target, it can also be lowered by natural supplementation with DHEA.

 

 

 

[ta5]

Bad news for Lithium. I don't think this has been posted yet. It's from a few months ago.

 

J Clin Psychiatry. 2017 Feb;78(2):e139-e145.

Association Between Lithium Use and Risk of Alzheimer's Disease

Cheng C1,2, Zandi P3, Stuart E3,4,5, et al.

OBJECTIVE: Current evidence for the association between use of lithium and risk of dementia is mixed. The objective of this study was to assess the risk of Alzheimer's disease associated with use of lithium.

METHODS: A population-based, nested case-control study was conducted using data from the National Health Insurance Research Database in 2002 covering 24.5 million beneficiaries of the Taiwan National Health Insurance Program from January 1, 1997, to December 31, 2009. A total of 2,548,625 older people were included in the study cohort. We analyzed 63,347 cases of Alzheimer's disease (ICD-9-CM codes 290.0-290.3, and 331.0) and 2 controls per case matched by age, sex, and index date (the date of the first AD claim). Conditional logistic regression was performed, adjusting for health care utilization, use of other common mood stabilizers (valproic acid and carbamazepine), hypothyroidism, type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease, epilepsy, schizophrenia, and bipolar disorder.

RESULTS: We identified 63,347 cases with Alzheimer's disease and 126,694 controls. The adjusted odds ratio (aOR) of Alzheimer's disease risk with lithium use was 1.79 (95% confidence interval [CI], 1.34-2.38) in the general population. However, when we restricted the analyses to patients with bipolar disorder to minimize potential confounding by indication, lithium was not associated with Alzheimer's disease risk (aOR = 1.36; 95% CI, 0.89-2.09), and there were no apparent trends of greater risk with increasing duration or dose.

CONCLUSIONS: These findings do not support an increased or decreased risk of lithium use with Alzheimer's disease when taking into account potential confounding by indication. Further investigations of the effect of lithium with dementia need to consider the influence of confounding by indication.

PMID: 28002662

 

 

[mag1]

Warburg again?

 

https://www.ncbi.nlm...pubmed/26766547

[MikeDC]

High fat diet increases NAD+. NAD+ is probably the mechanism of action.

[Heisok]

Thanks for the study. Based on the conclusion from your quote, I am not sure if the study is bad news for Lithium. Did you by any chance delve deeper into the study? or Did somebody else who would care to comment?

 

Thanks.

[resveratrol_guy]

Warburg again?

 

https://www.ncbi.nlm...pubmed/26766547

 

Hi mag1, good point. Here's 2c from someone who has tried every neurologically oriented diet in the book, more or less. Some of this is a repeat, but I think it bears repeating...

 

If only it were the Warburg effect. Cancer cells become cancerous in part because they learn to obtain energy from the glycolytic pathway. This process makes them overly reliant on glucose metabolism. But in the AD brain, this pathway is insufficiently activated to compensate for impaired glucose metabolism and sensitivity. (This would seem to involve damage to PDH, for one thing.) As a result, some neurons die due to poor maintenance and impaired waste efflux, while others enter a senescent state.

 

A ketogenic diet can often relieve this condition via the provision of acetoacetate and/or beta hydroxybutyrate, which bypass PDH to provide energy. From what I've seen of Dale Breden's work, for example, I must say I'm impressed with the approach.

 

Personally, as someone with probably impaired zinc transport, it just doesn't work. The reason is that protein intake on this diet is necessarily quite a bit higher, and richer in glutamic acid, than would be the case on a low-calorie but sugar-rich vegan diet. As a result, glutamate runs amok in the brain, resulting in excitotoxicity. Zinc gluconate can ameliorate this condition, but not to a sufficient extent, at least in my rather mild case. Cat's claw works better, but it crushes dopamine levels required for mathematical thinking and visualization, so in my own line of work it's not a longterm solution.

 

We can sort of choose between the aforementioned 2 diets. In one case, a high-ish protein intake probably results in elevated IGF1 over time. In the other, IGF1 is low (ideally, very low) but fasting glucose may eventually reach diabetic levels. From a cancer standpoint, if Laron syndrome is any clue, this is actually just fine because we need both elevated blood glucose and normal or higher IGF1 to create malignant tumors. (I actually just had an IGF1 test to see how well my protein restriction is going. We'll see.)

 

In all this, we have to remember that the most successful AD prevention methodology of all time was apparently drinking a few juices per week, if the Kame study is to be believed. Personally, I've taken to buying the more expensive, lower-sugar "greens" powders (not from China), so I can get the benefits of obscure fruits, veggies, and berries, but without the sugar or the hassle of juicing tons of fibrous material. (Beet powder is particularly helpful, I notice.)

 

The only other thing I have to add in this vein is that I've noticed that hydrogen water seems to help me sleep. It could be coincidence, so I plan to retest this soon. That matters because, in theory, it could potentially prevent the aforementioned excitotoxicity, thereby allowing zinc-impaired people like me to switch to and remain on a ketogenic diet. We'll see.

[MikeDC]

NAD+ precursors such as Niagen are the best at preventing Alzheimer's.

[mag1]

res, I have been very interested in PMID: 25579853 of late.

Bring glucose levels way way down.

 

This would be such a great test of the entire metabolic approach to cancer.

Seems like a really good to try out, though in most extreme implementation

would need to be done in an ICU; probably best not to be that extreme and

just bring down glucose somewhat more moderately.

Edited by mag1, 25 May 2017 - 11:45 PM.

[ceridwen]

I've just ordered some zinc gluconate. I found cats claw does nothing for me. Since falling ill my maths has been non existent.Strangely decided to give up all juices this week and felt myself getting much worse. I had up to that point been drinking rather an excessive amount of juice having found this really hard to give up.Does this mean I should start drinking them again. I have to say a low calorie high sugar diet sounds much more natural to me. How low is low calorie? How many calories a day? I hate beet juice though I'm more of a citrus juice person really. I'm getting really frightened again by the speed of decline this week since I stopped drinking them. Sounds like a good idea these "greens" powders but I was more intelligent on Orange juice with bits in it. Obviously I haven't tried "greens"but may look into this today.
The only other things I found was the idea of spending a month up a mountain somewhere. Sounds like a fun if dangerous? retreat possibly in August sometime or doing yoga for 45 minutes a day for 3 months. I read an article that said it can cure diabetes.

[ceridwen]

Giving up juices seems to be making a significant and frightening difference. I'd better start taking them again.

[ta5]

PQQ, Blueberry, Green Tea, Carnosine, and Vitamin D:

 

Heliyon. 2017 Apr 4;3(4):e00279. doi: 10.1016/j.heliyon.2017.e00279. eCollection 2017 Apr.

Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer's disease.

Sawmiller D1,2, Li S2,3, Mori T4, Habib A2, Rongo D2, Delic V5, Bradshaw PC5, Shytle RD6, Sanberg C7, Bickford P1,6, Tan J1,2.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II), containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis) in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks, starting at 3 months of age, after which behavioral and neuropathological endpoints were determined. The data from behavioral test batteries clearly revealed that dietary supplementation of Nutra II effectively ameliorated the motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II also protected mitochondrial function in 5XFAD mice brain, as evidenced by declined ROS levels and membrane hyperpolarization, together with elevated ATP levels and respiratory states. Interestingly, while Nutra II treatment only slightly reduced soluble Aβ42 levels, this formulation significantly impacted tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD mouse brain. Taken together, these preclinical findings confirm that mitochondrial function may be a key treatment target for AD and that Nutra II should be further investigated as a potential candidate for AD therapy.

PMID: 28413833

 

NT020 is "A nutraceutical combination of blueberry, green tea extract, carnosine, and vitamin D3 (a proprietary formulation known as NT-020)".

[ceridwen]

Mice cured again. Lucky mice