1230 replies to this topic

[Manwhoworkstoomuch!]

The side effects of Aducanumab are water on the brain and cysts in the brain. I don't think that would be worth it. There must be other ways...

 

That sounds bad.

[albedo]

Cattaneo A, Cattane N, Galluzzi S, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2016;49:60-68.

 

"...Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation..."

[Der Springende Punkt]

Nice find, albedo!

[Iporuru]

I couldn't find these posted before:

 

Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease

 

http://www.sciencedi...14488616303971

 

 

Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment

 

http://onlinelibrary.../cns.12655/full

 

 

Edited by Iporuru, 27 November 2016 - 09:41 AM.

[Der Springende Punkt]

Related to albedos gut microbiota paper: A recent trial (though from Iran and with design limitations) found a benefical effect of probiotics in severe Alzheimer's patients:

 

Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

[elfanjo]

Didn't read the whole thing.
Has lithium supplementation been explored here? Studies are showing promising results.

[mag1]

Fungal cause of AD?
https://www.ncbi.nlm...pubmed/27872620

 

 

"Low systemic toxicity of β-ecdysone further extends the applicability of the compound as functional

food and dietary supplement for disease management"
 

Is there an online supplier of this?

 

https://www.ncbi.nlm...pubmed/27871792

 

​"...the effect of trans-crocetin, an active constituent of Crocus sativus L., to restore in vitro the reduced ability

of AD patients' monocytes to degrade amyloid-β_(1-42) (Aβ₄₂). CD14⁺ monocytes..."

 

https://www.ncbi.nlm...pubmed/27865556
 

Edited by mag1, 27 November 2016 - 05:19 PM.

[TRUGAN]

Fungal cause of AD?
https://www.ncbi.nlm...pubmed/27872620

 

 

"Low systemic toxicity of β-ecdysone further extends the applicability of the compound as functional

food and dietary supplement for disease management"
 

Is there an online supplier of this?

 

https://www.ncbi.nlm...pubmed/27871792

 

​"...the effect of trans-crocetin, an active constituent of Crocus sativus L., to restore in vitro the reduced ability

of AD patients' monocytes to degrade amyloid-β_(1-42) (Aβ₄₂). CD14⁺ monocytes..."

 

https://www.ncbi.nlm...pubmed/27865556
 

 

 

Maybe its in here. I dont know.

 

http://us.myprotein....e/10982651.html

[mag1]

Phase 3 results for MB.

Results are even stranger than first reported.

Apparently the "placebo" 4 mg monotherapy arm had a response.

 

Would it not be more plausible to attribute this to the highly unusual study design (i.e. patients knew and chose

to be on the non-treatment arms and a very high percentage of this group dropped out of the study)?

 

All the non treatment arms (monotherapy) including placebo 4 mg had large "treatment" effects.

Wonder what such a treatment effect might be if they treated with 0 mg MB and added a true placebo to discolor the urine.  

https://www.ncbi.nlm.../?term=27863809

[mag1]

​Is Beta-Ecdysterone chemically equivalent to β-ecdysone​?

I think they are in the same class, though I am not totally sure.

 

"The present study demonstrates the applicability of a phytoecdysteroid, β-ecdysone,

as a multi-potent agent in AD therapeutics. β-ecdysone strongly binds to the active site cavity of BACE1

with calculated dissociation constant of 1.75±0.1μM" from article url above. 

 

From what I understand β-ecdysone​ is derived from an insect hormone.

"Ecdysone is a steroidal prohormone of the major insect molting hormone 20-hydroxyecdysone,

which is secreted from the prothoracic glands. Insect molting hormones (ecdysone and its homologues) are generally called ecdysteroids." wiki

 

Um, the ew response would be very appropriate about now.

 

Is this actually used as a functional food somewhere?

Edited by mag1, 27 November 2016 - 06:27 PM.

[TRUGAN]

​Is Beta-Ecdysterone equivalent to β-ecdysone​?

I think they are in the same class, though I am not totally sure.

 

"The present study demonstrates the applicability of a phytoecdysteroid, β-ecdysone,

as a multi-potent agent in AD therapeutics. β-ecdysone strongly binds to the active site cavity of BACE1

with calculated dissociation constant of 1.75±0.1μM" from article url above 

 

From what I understand β-ecdysone​ is derived from an insect hormone.

"Ecdysone is a steroidal prohormone of the major insect molting hormone 20-hydroxyecdysone,

which is secreted from the prothoracic glands. Insect molting hormones (ecdysone and its homologues) are generally called ecdysteroids." wiki

 

Um, the ew response would be very appropriate about now.

 

Is this actually used as a functional food somewhere?

 

 

Im not sure and I didnt spend a lot of time with it but the following link might be helpful.

 

https://examine.com/...s/ecdysteroids/

 

 

Also, I saw it in a body building forum. 

 

http://www.bodybuild...hfacts_ecdy.htm

[Avatar of Horus]

Lilly Announces Top-Line Results of Solanezumab Phase 3 Clinical Trial

Nov. 23, 2016

https://investor.lil...leaseid=1000871

 

Eli Lilly and Company (NYSE: LLY) today announced that solanezumab did not meet the primary endpoint in the EXPEDITION3 clinical trial, a phase 3 study of solanezumab in people with mild dementia due to Alzheimer's disease (AD).

Patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo (p=.095), as measured by the ADAS-Cog14 (Alzheimer's Disease Assessment Scale-Cognitive subscale).

... Lilly will not pursue regulatory submissions for solanezumab for the treatment of mild dementia due to Alzheimer's disease.

"The results of the solanezumab EXPEDITION3 trial were not what we had hoped for and we are disappointed for the millions of people waiting for a potential disease-modifying treatment for Alzheimer's disease," said John C. Lechleiter, Ph.D., chairman, president and chief executive officer, Lilly. "We will evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer's pipeline assets."

...

About Solanezumab
Solanezumab is Lilly's phase 3 monoclonal antibody being studied as a potential therapy for people with mild cognitive impairment due to Alzheimer's disease ...

[mag1]

Yes, though it is interesting that recently they decided to double down on sola and start a phase 3 in prodromal AD.

 

https://clinicaltria...anezumab&rank=2

[Avatar of Horus]

Yes, though it is interesting that recently they decided to double down on sola and start a phase 3 in prodromal AD.
 
https://clinicaltria...anezumab&rank=2

Yes, btw this 'mild case' trial was already a "doubling down" from a previous one for advanced Alzheimer patients.


Here is a recent Nature article about the state of things, including solanezumab:
How to defeat dementia
Elie Dolgin
09 November 2016
http://www.nature.co...ementia-1.20949

Some coverage on the forum:
The State of the Mainstream of Dementia Research - BioscienceNews
http://www.longecity...entia-research/

[mag1]

Avator, you are correct.

We should call it a double double downing.

 

Seems like Lilly knows something everyone else missed.

They started the prodromal phase 3 in July and it will cost them quite a bit more money.

The market thinks sola failed, perhaps it didn't?; at least we're not sure about those earlier than mild AD.

 

They hit a sub 10% p value in their recent phase 3 and their was also a lowish p value on the previous analysis.

It will be tough waiting 5 years to see how this plays out.

 

Expedition3 presentation will be live streamed to the web from the CTAD conference San Diego, USA – December 8-10, 2016.
Wonder if they will be any sub-groups that might have benefited?

​apoe epsilon 4, the mildest patients, ... There are so many opportunities to go fishing. 
 

 

 

 

 

 

 

  

[YOLF]

The side effects of Aducanumab are water on the brain and cysts in the brain. I don't think that would be worth it. There must be other ways...

 

Is this true, could the water on the brain effects be ameliorated by increasing creatine or testosterone?

[mag1]

Anyone out there up for an n=1 experiment to save the planet from the approaching Alzhageddon?

 

 

http://www.alzforum....-lowers-av-mice

 

Plan is:

1. Check amyloid levels, perhaps with the amyloid retinal scan.

2. Listen to / watch 40 Hz gamma frequency for 1 hour per day (Neuroprogammer, light and sound machine, anyone have a good url for this?).

3. Repeat step 1.

4. Report to the people.  

Edited by mag1, 08 December 2016 - 02:34 AM.

[tunt01]

Could restoring gamma power prevent pathology? The MIT researchers used a virus to express the light-sensitive channelrhodopsin-2 in fast-spiking parvalbumin-positive (FS-PV) interneurons of the CA1 region of the hippocampus in 5XFAD mice. These inhibitory interneurons help generate gamma waves. Through an implanted fiber-optic wire, they pulsed light at 40 Hz to open the rhodopsin channels and drive gamma waves. This does increase overall activity and, at the same time, synchronize it. After an hour, total Aβ40 and Aβ42 in the hippocampus fell by 53 and 45 percent, 

 

 

Very cool, but the implant was in the CA1 region of the hippocampus.  I'd love to know how reproducible that is.  Holtzman seems interested in it.  He's one of the best alzheimer researchers around.

[mag1]

I think that they also simply used gamma frequency sound with the mice and they received the same result.

It would be so much easier if people could just put an app on their computer screen and now have to worry about AD instead of having to go through brain surgery.  

 

I have an infinite loop of beta frequency strobe flashing with beta audio through the day on my computer.

What might that be doing to my brain?  

Edited by mag1, 08 December 2016 - 02:41 AM.

[mag1]

Hmm, police use tactical strobe flashlights?

Not aware of this.

 

Below website notes that this could cause fatal response in epileptics.

Interesting that the police found that 7.8 Hz was the best frequency.

Wonder what the tactical response of High Beta or Gamma might be on an agitated apprehendee? 

 

 

http://www.policemag...flashlight.aspx

[mag1]

CTAD starts tomorrow in San Diego goes until Saturday.

Looking out for the second phase 3 for LMTX.

 

Top line is already known to be positive.

Big question is whether this is a truly legitimate positive or only a bogus positive caused by the strange nature of the study design.

[mag1]

I believe an extended quote is in order.

 

In another experiment the researchers merely put the mice in a dark room and exposed them to gamma frequency strobing.

This treatment reduced amyloid (by up to 60% in a week with 1 hour daily treatments) and reduced phosphorylated tau and reduced microglial activation.

No brain surgery required.

Not bad.

 

 

"Next, the researchers wanted to drive gamma oscillations in a less invasive way. They placed three-month-old 5XFAD mice in a dark chamber and, for one hour, flashed a dim LED light at their eyes at 40 Hz to generate gamma frequency waves in the visual cortex. Lo and behold, both Aβ42 and Aβ40 levels dropped in this brain area by 58 percent. This strategy to lower soluble Aβ worked in APP/PS1 and wild-type mice, as well. In six-month old 5XFAD mice that had deposited plaques, a week of this treatment caused 65 percent of them to vanish. Neither random, 20, or 80 Hz light pulses reduced Aβ. In addition, microglial cell bodies swelled, their processes shortened, and they accumulated more Aβ inside. Interestingly, the same light-pulse treatment also reduced phosphorylated tau in the visual cortex of TauP301S mice by 40 percent, and activated microglia in those mice as well."

 

http://www.alzforum....-lowers-av-mice

 

[tunt01]

That's fricking amazing and crazy if true.  I would have never though of that as a mechanism to trigger phagocytic clearance of amyloid beta.  Although it says, "In this brain area".  I would want to see slices of everything, hippocampus, etc.  I hope they aren't just talking about the visual cortex.

Edited by prophets, 08 December 2016 - 03:33 PM.

[ceridwen]

I have App/PS2 would it work for me?

[mag1]

Please prophets decorum, decorum!

Though, I do share your sentiment if not your vocabulary.

 

Of note is that this is not a journal of dubious reputation, it is THE journal of Science.

One would expect that they did not liftover figures from other articles or commit out and out scientific fraud.

 

Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 8; 540, 230–235.

 

This result should not be considered overly surprising. It has long been known that the delta sleep state helps reduce amyloid levels.

What is quite surprising is that they are using a high frequency, gamma, and seeing amyloid reduction.

 

That does not make sense.

High neuronal activity should lead to high amyloid production.

Research will likely investigate this question, though it is possible that gamma frequency not only increases amyloid production,

but also and more strongly increases amyloid degradation.

 

 

If I had done the experiment, I would have tried delta entrainment.

It is possible that delta entrainment would help, though 20Hz beta and super high 80 Hz seemed to make things worse.

 

 

This could have profound implications for AD.

 

Moderate lifelong amyloid reduction is known to have a large effect on AD pathology.

​"Cells that received the protective variant churned out about 40 percent less Aβ40 and Aβ42 than did cells containing wild-type APP."

http://www.alzforum....loid-hypothesis

 

Typically those without such a variant (which is over 99% of people) will inevitably develop Alzheimer pathology by their 90s.

 

I also wonder what this might mean for the pharmaceuticals in development for AD. Some of these drugs have frequent side effects.

For example, one of the antibodies had brain swelling in over 50% of one subset of patients.

 

It is not clear whether there would be any side effects for typical people (i.e. non-epileptics) from strobing therapy.

 

A large hurdle here might be the question of how to patent this idea.

Could a really good treatment be derailed simply because there would be too many free riders?

I suppose that they could spend a few decades finding a chemical way to entrain to gamma frequency, though I suppose that

every nation would be close to bankruptcy if they were to do so.

 

The big question for me is how could they possibly have never done this experiment before?

 

 

 

 

Edited by mag1, 08 December 2016 - 04:24 PM.

[mag1]

cerdiwen, it might not.

 

The current thinking is that once symptoms emerge amyloid lowering might no longer be very helpful.

This is still somewhat of an open question, though.

 

It appears that amyloid lowering therapy might only be helpful at the earliest stages or perhaps even 5-10 years before symptom onset.

It probably would not hurt to try.

 

Does anyone have a url for an online gamma frequency strobe.

Perhaps there is an app that will do this?

 

 

Edited by mag1, 08 December 2016 - 04:31 PM.

[mag1]

I am wondering whether any gamma frequency entrainment would do the trick?

Audio, vibration?

Audio would probably be easier for most people.

 

One would think that entrainment is entrainment.

[tunt01]

 

This result should not be considered overly surprising. It has long been known that the delta sleep state helps reduce amyloid levels.

What is quite surprising is that they are using a high frequency, gamma, and seeing amyloid reduction.

 

 

It's not like sleep per se.  I think the way to look at this intervention is that it is closer to some form of meditation.

 

However, when the monks were told to generate an objective feeling of compassion during meditation, their brain activity began to fire in a rhythmic, coherent manner, suggesting neuronal structures were firing in harmony. This was observed at a frequency of 25–40 Hz, the rhythm of gamma waves. These gamma-band oscillations in the monk’s brain signals were the largest seen in humans (apart from those in states such as seizures). Conversely, these gamma-band oscillations were scant in novice meditators. SOURCE

 

 

It reduces amyloid beta generation and improves clearance via microglial.  Very interesting.

 

They started a company to pursue the research.

[mag1]

One does have to wonder how this technology could fit as a money maker.

​How can you charge big dollars for flashing lights?

 

Might need to call on the Longecity community to step up and help out.

Once we have a good simple and cheap amyloid measurement tech (amyloid retinal scans)

we could start experimenting with gamma entrainment. This would be great. 

 

I have gamma frequency strobing on my computer right now.

Probably will have it on 12 hours a day from now on.

 

I would have to guess that there is a free app that could do this as well.

 

For audio entrainment, all you need to do is go to the below url, enter 500 for left ear and 540 for the right and

you have gamma frequency audio entrainment. (This only works if you are wearing headphones.)

 

Edited by mag1, 08 December 2016 - 06:40 PM.

[tunt01]

One does have to wonder how this technology could fit as a money maker.

 

I have gamma frequency strobing on my computer right now.

Probably will have it on 12 hours a day from now on.

 

 

Anything that has to be approved by the FDA and delivered as a service by a licensed medical doctor is going to require high costs to a patient population and deliver high margin profits to a provider.

 

12 hrs a day seems overkill to me.  Maybe as an 'attack dose' in the first day or two.  Exercise prevents alzheimers, that doesn't mean we want to go run for 12 hrs today.  Everything in moderation.