NY Times article on theory that parasitic infection may be reason APOE4 was once protective

[cdamaden]

https://mobile.nytimes.com/2017/07/14/o ... erica.html



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[ru442]

Interesting read, and hopefully a promising lead for a treatment of some kind. I was especially surprised by the number of comments (181 as of now), given the subject matter and the fact the article was published today. It makes me feel good that there is broader awareness of APOE4, and folks are taking notice.

ETA: And the comments discussion is pretty spirited... lots of differing opinions on the science behind it all.

[floramaria]

Thank you, Chris. About 1/2 way through the article I was considering taking a quick stroll down to our local stream and taking a few big gulps, which could almost certainly guarantee me both giardia parasites and bacterial infections. Fortunately, I read to the end of the article. Very interesting. Thanks for posting it. The idea that the ApoE4 must have provided some benefit in the times when it was the only form of ApoE makes sense and I have heard that theory discussed, but the work with the Tsimane people shows that protective benefit in action now.

[ru442]

I was considering taking a quick stroll down to our local stream and taking a few big gulps, which could almost certainly guarantee me both giardia parasites and bacterial infections

LOL! I was thinking the same thing about the river in my backyard, but then.....

[floramaria]

HAHAHA!!!
Happy I am not the only one!!

[ajackson]

Interesting article. Thanks for sharing! A couple of years ago I took my adult kids to Costa Rica. The tour guide at Manuel Antonio Nat'l Park demonstrated drinking from a stream of water that would kill any of the rest of us from the US. He said he had to get used to it slowly but that the native people who drink this water are never sick. Maybe it is the parasites? As we find that the gut microbiome is so important for brain health it would make sense that the parasites could be protective. I've had Giardia though and really don't want it again.

[lumia]

I wonder this hypothesis only applies to parasites, or infections in general? The latter would be easier to mimic.

[Julie G]

I had an interesting conversation with Dr. Bredesen about this paper (and NYT article) yesterday. He's finds it intriguing and has an upcoming lunch scheduled with one of the authors so that they can dive into the whole ApoE4 aspect. Dr. Bredesen is very careful to point out that this paper only examined a parasite-causing dementia. Extrapolating to Alzheimer's may be stretch. The paper's authors are suggesting, however, that E4 carriers, who had been exposed to parasites did appear to do better cognitively than E4 carriers who weren't. There are many implications and overlaps with Dr. Bredesen's CIRS findings. This may explain why E4 carriers, who are positive (hand waving!) aren't as severely impacted as the other APOE genotype. Let's ask him to talk about this more in San Diego... and then we can go eat some worms .

[Lucy5]

I thought this was an interesting read; Rudy Tanzi & coauthor response to and reflections on the NYT article discussed in this thread:

Dr. Robert Moir & Professor Rudolph Tanzi:
apoE4 and Alzheimer's Disease

Cure Alzheimer’s Fund (CureAlz) has asked for our comments regarding the recent op-ed in the New York Times on apoE4 and Alzheimer's disease (AD) that has generated so much public interest.

It is terribly important to raise and maintain public awareness of the research efforts to develop treatments for this devastating modern plague that is afflicting our elderly. This article certainly is a welcome addition to improving awareness and we believe it makes a positive contribution. However, we do think some clarifications are needed concerning impressions about the cause of the disease that readers may be left with after reading the article.

The article may give the impression that the discovery of a role for immunity in AD is a recent advance. However, we, at the Massachusetts General Hospital (MGH) Genetics and Aging Research Unit, have been working on the role of immunity in Alzheimer’s disease for over a decade. A large part of that work has been funded by CureAlz, and indeed, may not have happened without that support. Similarly, our Unit at MGH has been testing possible drugs that target immune pathways and has a candidate compound set for human clinical trial that appear to “calm” the overactive immune cells mentioned in the article. This work was also funded in large part by CureAlz. Lastly, it has been known for some time that amyloid alone is insufficient to cause AD – it must be accompanied by inflammation. That does not mean amyloid is the wrong target.

The CureAlz funded study we reported in May 2016 shows that the amyloid generated in Alzheimer’s disease is normally part of an immune pathway that protects against infection. The amyloid entraps and entombs invading microbes. Thus, a role for APOE4 in protecting aborigines from parasites most likely stems from the excess beta-amyloid it engenders in the brain, leading to more antimicrobial protection. The resulting increase in amyloid generation would then later increase risk for AD. The writer did not cover this critical point. The findings in the aborigines are also not evidence that amyloid is irrelevant. In fact, this is a classical example of a phenomena known as evolutionary antagonistic pleiotropy in which something is beneficial early in life (APOE4 and associated increases in beta-amyloid protecting against parasites), but has costs later in life (increased risk for AD). Finally, we consider the findings discussed in the article a significant contribution to the field and reaffirm the potential of the research strategy that CureAlz has been helping to craft for nearly a decade.


Signed,
Dr. Robert Moir, and
Professor Rudolph Tanzi, Chair of Cure Alzheimer’s Fund Research Consortium

[Julie G]

VERY interesting, Lucy! I definitely agree with Dr. Tanzi and colleague that beta-amyloid is a part of this same E4 immune upregulation. Can't wait to see you soon. xo