HDL plays a pivotal role in preserving cognition

[Julie G]

HDL and cognition in neurodegenerative disorders.
http://www.ncbi.nlm.nih.gov/pubmed/25131449

New paper suggesting HDL is key to preserving cognition. I'd love to see full-text, Stavia

Abstract
High-density lipoproteins (HDLs) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function.
Copyright © 2014 Elsevier Inc. All rights reserved.

[LillyBritches]

Niiiiiccccceeee, mama! Thanks! EVOO 4-ever.

[Stavia]

hdl.pdf

here you go

[zig]

Thanks for posting.

I've seen it suggested in a few places that Apoe4 can cause low HDL. The only study I could find that confirmed this was a mouse study so not sure how valid it is but I seem to have stubbornly low HDL despite an improvement in all my other biomarkers with a diet change

Does anyone else have this issue with HDL? It would almost seem I need to eat more fat in an effort to improve this

Evidence for differential effects of apoE3 and apoE4 on HDL metabolism.

http://www.ncbi.nlm.nih.gov/pubmed/12401887

We present a murine model that examines the effects of macrophage-produced apolipoprotein E3 (apoE3) and apoE4 on VLDL and high density lipoprotein (HDL) metabolism. Mice expressing apoE3 on the Apoe(-/-) background had substantially lower VLDL levels than mice expressing apoE4. In addition, there were differences between the HDL of apoE3- and apoE4-expressing mice. Apoe(-/-) mice have low levels of HDL. Low level expression of either apoE3 or apoE4 was able to restore near-normal HDL levels, which increased dramatically when the mice were challenged with a high-fat diet. ApoE4-expressing mice had smaller HDL than apoE3-expressing mice on both chow and high-fat diets. In addition, plasma from apoE4-expressing mice was less efficient at transferring apoA-I from VLDL to HDL and at generating HDL in vitro than that from apoE3-expressing mice. Thus, we present experimental evidence for differential effects of apoE3 and apoE4 on HDL metabolism that supports epidemiological observations made in humans, which suggested that individual homozygous for the epsilon 4 allele had lower HDL than others.

[Doctor Lost]

well unfortunately My HDL has been consistently low, to go with my E3/E4

[zig]

well unfortunately My HDL has been consistently low, to go with my E3/E4

Have you found evidence these are related ? It seems suggested in a few places

Mine is low as well

[Gilgamesh]

Wow. This is an important topic. Thanks to Julie for starting it, and Stavia for the paper.

There's been a lot of work on the lipidation status of ApoE. Read, for ex., the first few paragraphs of the following:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493297/

I'm starting to think that we might well consider HDL to be a small molecule corrector. I'm going to contact some of the key researchers involved to see what they think about HDL and ApoE4.

A lot of things are falling into place for me. Exercise is esp. good for ε4-carriers. Why? Because it increases HDL, which "corrects" our ApoE, something less needed for non-carriers. And ethanol: it doesn't help us because, unlike in non-carriers, it doesn't raise HDL much in us.

Cool and important stuff!

GB

[Gilgamesh]

Key theoretical questions:
- Is HDL as important as we, or at least I, think?
- Might it primarily be HDL-2 that matters?

Key practical question (assuming HDL really matters):
- How do we best raise HDL (or HDL-2, if that's the kind that matters)?

I know exercise and CR work very well, and there's tons of research to support these two approaches (the former is esp. well-supported for ε4s).

I'd love to see an analysis of CR in ε4s. (I'm working on that -- the data might actually already be available, just not published.)

As far as dietary constituents are concerned (something of great interest to ~90% of the people currently posting frequently to this group), I'd love to see a study -- or a meta-analysis -- comparing dietary constituents that had the following characteristics:

- healthy, normo-weight subjects.

- longer than a year (we know the benefits of high-fat diets often diminish after a year or so).

- isocaloric diets, or weight maintenance level of intake.

- high-fat diets that have good fat, and high carb diets that have good carbs.

- ε4-carrier vs. non-carrier.

GB

[Gina99]

Could someone clarify the def. of low HDL. My lab indicates a ref range of 30-90 mg/dL as normal. Is this similar to other levels, where 70-90 range is optimal (i.e. Vitamin D3)? Or is it taken as the whole picture with the remainder of the lipid profile? My HDL has been consistently in the 43-53 range over the past 8 years.

[Welcomeaboard]

I like the way you are thinking on this idea GB. Try and create a protocol and see if funding could be arranged for a study based on that protocol if it had not been done already. Or entice the researchers to think about it and perhaps arrange for it to happen.