HDL particle size and Alzheimers

Recent research has found a correlation between higher levels of large size HDL particles and Alzheimers, and higher levels of small size HDL particles to be protective. So, very high levels of HDL, eg higher than 80, can be a risk factor, but perhaps mitigated if the particle size distribution tends to small size.

For years I thought that my numbers were great – OK LDL, super high HDL, the “good” cholesterol, and then I learned (thank you Peter Attia-- he seemed to be the first to shine a light on this) somewhat high LP(a), and now this news about high levels of HDL and Alzheimers. (Promethease says my highest risk is colon cancer, because of an APC mutation – but I can’t even be bothered to worry about that given the other stuff. )

As a 75 YO female with mother, aunt and grandmother centenarians who have/had Alzheimers, I am terrified. My HDL is about 115 to 120. Added to the above-- I have quite low insulin, another risk factor for Alzheimers. My “behaviors” are pretty good; much better than theirs, but the mountain of genetic/phenotypic risk is daunting.

I would like to have an HDL particle size assay – anyone have any suggestions how/where to have this done?

And any other thoughts would be so appreciated.

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This checks out. High insulin, more cancer. Alzheimer’s patients have lower rates of cancer. Low insulin, less cancer, more AD.

Which is why I’m a big believer in polypharmacy. Get to your goals with drugs, as selectively as possible, side stepping negatives and compensating.

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Insulin sensitivity, indicated by low insulin, is a sign of metabolic health, and I would have thought should be associated with a lower, not higher, risk of AD.

Metabolic syndrome is characterized by insulin resistance and high insulin levels, and is a risk factor for AD. I don’t like the term “Type 3 Diabetes” for AD because I think we know AD is way more complicated than that, but again that ties high insulin to AD.

@CronosTempi , what in your view do I have wrong here?

I don’t know about “wrong”. But there simply are different phenotypes. It’s not the case that every time glucose levels are high it’s because of insulin resistance. It can also be due to insulin insufficiency. Your pancreatic beta cells are not producing enough insulin or it’s getting blocked for whatever reason. Perhaps that kind of phenotype is more prone to AD - I don’t know. The relationship between insulin, glucagon, gluconeogenesis, glucose is complicated. There are a lot of moving parts. Which is why first and foremost we observe outcomes, and only then attempt to explain that mechanistically. The associations appear to be - more AD, less cancer. Why - who knows.

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Yes: different phenotypes. I am convinced of this, that we are all on a spectrum from anabolic to catabolic. Just as there are body types: mesomorph, endomorph, ectomorph, there are genetic profiles that are high growth or low growth. Synthesizing everything I have read, a drug like rapamycin that reduces mTOR, thus reducing protein synthesis and growth, is a good fit for someone with an anabolic phenotype, who could benefit from a push toward slower growth. I myself am the catabolic type --slow growth, small stature, early menopause.

And, to your point about insulin: I am convinced that my low insulin levels are a result of a mutation in the genes that control production of glucokinase. I am quite insulin sensitive: I just don’t produce very much insulin. This is not classic diabetes, but some sort of rare variant, caused solely by genetics (and can be confirmed through genetic testing for glucokinase mody, though docs and insurance won’t do the testing because there is no treatment required. GKM manfests simply as a pre-diabetic glucose level that does not progress.

That is why I lit up when I read about intranasal insulin as a possible therapy for preventing or forestalling AD. It makes perfect sense: too little endogenous insulin available to the brain, but the IN insulin goes right into the brain via the olfactory and trigeminal nerves, and does not get into the body at all. I wrote to a leading practitioner/clinician expert on insulin and type 1 DM, laid this out, and asked for his thoughts on IN insulin. He responded – keep using it. He did caution that I should have an effective delivery instrument, and I suspect that the little Snoot bottles are far from efficient but that’s all I can find . . .

Also, my conviction that I am this catabolic type made me decide not to take rapa – I do not need a push toward reducing mTOR, reducing growth.

I feel like a spoiler in this community of avid rapa users. I do believe it is a fantastic intervention, and I gave my stash to my son who seems to be a more anabolic type, very much like his father. But I believe that we need a model for prescribing / taking drugs that takes this anabolic/catabolic paradigm into consideration. One size does not fit all.

I wonder what is the opposite of rapamycin that I should be taking. My tiny mother, before she developed dementia, continually craved red meat, and she consumed massive quantities, dripping blood. (no fruits or vegetables unfortunately). I don’t want to eat red meat but have started taking leucine.

So yes, there are these types – high growth, higher cancer, etc, and low growth – long life, lower cancer, higher Alzheimers. I believe that some day all therapies will be prescribed based not merely on the symptoms a patient presents, but on an assessment of phenotype.

I am so grateful to this forum and all the information out there that enabled me to figure this out.

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Lipoprotein Fractionation Test, NMR

I don’t know if this is what you are looking for, but this test, which is available from Ulta Lab
It is a more definitive lipoprotein test than the typical one doctors order,
Currently, the price is $45.95, and usually, you can get 20% off your first order.
You can choose to have your test done at LabCorp or Quest Diagnostics.

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Thank you Desert Shores! I just tried to order and learned that residents in NY, NJ and RI cannot order directly from Ulta or Quest but I might be able to get my PCP to write an order.

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@Deborah_Hall - I think you may find the new thread I created quite illuminating. Your phenotype is discussed specifically - or if not your phenotype, at least a phenotype of people who have diabetes or high serum glucose with concomitant very low insulin production; these people are extremely hard to treat at present, and we have no good drugs for them. This might be changing and we now have insight into this condition. The new thread is about menin inhibitors.

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