Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Variant

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rep
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Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Variant

Post by rep »

IF I survive my lipid problem maybe there's hope for my mind. I searched but could not find that this had already been posted.
Since I have the bad MAPT polymorphism for the tau I am relieved that my Klothos variant may yet save my brain. (Grateful for my little 3% Ashkenazi Jewish roots, wherever they came from...)

From Gladstone, posted February 10, 2015 -

Protein Linked to Longevity and Enhanced Cognition Also Protects Against Alzheimer’s Symptoms
Increasing klotho in Alzheimer mice improved their cognitive function in spite of disease-causing proteins in the brain

http://gladstoneinstitutes.org/pressrel ... gainst-alz

This is actually great news even for those without the natural Klothos variant as it seems promising that they will devise a drug that is similar in effect.
“The next step will be to identify and test drugs that can elevate klotho or mimic its effects on the brain,” says senior author Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and the Joseph B. Martin Distinguished Professor of Neuroscience at UCSF. “We are encouraged in this regard by the strong similarities we found between klotho’s effects in humans and mice in our earlier study. We think this provides good support for pursuing klotho as a potential drug target to treat cognitive disorders in humans, including Alzheimer’s disease.”
I needed some good news today.
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by marthaNH »

Congratulations! Excellent news. You deserved some.
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by Stavia »

yay!!
...is Klotho Ashkenazi? I couldn't find it on my 23andme data. I'm 98.5% Ashkenazi...
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by asiagillett »

Ah yes the Klothos gene, named after the Greek fates, fitting huh how they name these things??? Stavia, I remember looking at this when I first found out my Apoe4/4 status. You should be able to see it on 23andme, RS9536314. I read somewhere once that being heterozygous is actually the desired pairing on this, so GT. I am the normal TT. GG actually looked worse, or "deleterious" if I remember.

Hopefully that helps you track it. I stopped looking at snp's remember but this is in my Apoe file from early on. So not sure if the fates cut my string on this one??? Ha ha.

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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by LillyBritches »

Hey, guys - yep - there are a couple of threads on this already. This is the most recent (before this one): :)

viewtopic.php?f=16&t=1214&p=12797&hilit=klotho#p12797

I'm GT. I have the variant, as do a couple of our community members (rep being one of them). It's a really, really good variant to have. I've been in touch with one of the head KLOTHO researchers and she does, indeed, think that this variant will be shown to override the deleterious impact of e4. It's powerfully protective. TT is neutral (most common), and GG is thought to be "bad."

I've also contacted Dr. Bredesen about it, and he concurs that the variant is a very good thing to carry, indeed.

Oh, and no. It's not associated with one being Ashkenazi.
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by Stavia »

Ok, not looking, I don't wanna know
(head in sand)
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by rep »

I am sorry. My apologies about the Ashkenazi part. I definitely got my wires crossed on that one. I can't even explain it.

But, still great news that they have a new target for drug development!
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by Stavia »

All good :)
There are apparently Ashkenazi longevity genes. I think I have at least one, saw it in a flash on that fateful Promethease data dump. I'm not going back to look. Don't wanna know.
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Re: Protein Linked to Longevity and Enhanced Cognition Also Protects Against AlzheiGreat News for Those with Klothos Var

Post by LillyBritches »

But, Stavia, think about how good you'll feel if you do have the variant. Same coin, different sides, though, so I completely understand not wanting to check. You're 100 times less compulsive than I.

However, I'm very happy I checked, and I'm not going to lie - that I have this variant (as do my mom and husband, oddly enough) has really lifted the dire straits of my knowing my e4 status.

I'm sure the paper has been linked before, but here it is. Dr. Dubal is the researcher with whom I corresponded:

http://www.cell.com/cell-reports/pdf/S2 ... 0287-3.pdf

Nota bene the variant relating to e4:
APOE ε4, the main genetic risk factor for Alzheimer’s disease (AD) (Verghese et al., 2011), did not contribute significant variance (Table S5), and including ‘‘cohort’’ as a covariate in meta-analysis did not alter results (data not shown). KL-VS carriers scored higher than non-carriers in each cohort and in meta-analysis of all cohorts (Figures 1A–1D; Table S5).

KL-VS Is Associated with Better Cognition Independent of Age, Sex, and APOE ε4 Allele Status
Meta-analysis showed that advancing age, male sex, and lower education decreased cognitive scores; KL-VS heterozygosity increased scores despite these effects (Table S5). Baseline cognition was not affected by APOE ε4, consistent with previous findings (Yaffe et al., 1997), though detrimental effects of APOE ε4 on cognitive aging might be revealed by longitudinal analysis (Deary et al., 2002; Yaffe et al., 1997). KL-VS did not differentially affect cognition by sex (Table S6), but there was a trend (Table S6) for its positive impact to decrease with advancing age (Figures 2A–2D).
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Post by Stavia »

But theres three options. Good bad n neutral. I'll be very sad if I have the bad variant. I don't wanna be sad.
The last modifying thing I looked up was COMT. Im good there. And I lucked out on zero methylation issues. Not pushing my winning streak any further.
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