Why Do Only Some People Suffer Alzheimer's Disease?

Alzheimer's disease might be argued to be a lifestyle condition, but it is not as much of a lifestyle condition as type 2 diabetes - it is not as reliably connected to lifestyle choices. Not everyone who lets themselves go, becoming fat and sedentary, winds up with a diagnosis of Alzheimer's disease, despite it being clear from the data and what is known of the mechanisms involved that both of those environmental circumstances are contributing risk factors. So why do only some people with the risk factors suffer Alzheimer's disease? Why do some people without the risk factors suffer from Alzheimer's disease? Is there anything useful to be learned at this stage from comparing the biochemistry of various groups with and without the condition?

These are questions very focused on how exactly the condition progresses, which stands a little in opposition to the strategy of attacking all of the known root causes of disease - in other words striving to remove all of the accumulated protein aggregates thought to cause the condition. In the case of Alzheimer's disease, that strategy hasn't been doing so well to date; the amyloid clearance field is a graveyard of failed clinical trials. Does this mean there is vital information yet to be discovered, or does it mean that the research community hasn't been clearing enough molecular waste, and both tau and amyloid must be reduced in the aging brain in order to see benefits? Arguments can be made either way.

The two primary histopathological changes to the brain due to Alzheimer's disease (AD) are the deposition of amyloid and tau. These two AD-related brain changes are the primary underlying causes of neurodegeneration and cognitive dysfunction which ultimately leads to dementia. As human longevity increases, and AD dementia increasingly becomes a major societal burden, finding pathways that lead to brain aging without AD pathologies (ADP) are critical.

Currently, much of the research has been focused on resilience or cognitive reserve, wherein the focus has been on discovering how and why individuals are able to remain clinically unimpaired or cognitively normal despite ADP. However, it is important to investigate, using surrogates of amyloid and tau pathologies via cerebrospinal fluid (CSF) and positron emission tomography (PET), why majority of individuals develop ADP as they age and how some oldest old individuals are able to age without significant ADP. The latter individuals are called "exceptional agers" without ADP.

There are three testable hypotheses. First, discovering and quantifying links between risk factors and early ADP changes in midlife using longitudinal biomarker studies will be fundamental to understanding why the majority of individuals deviate from normal aging to the AD pathway. Second, a risk factor may have quantifiably greater impact as a trigger and/or accelerator on a specific component of the biomarker cascade (amyloid, tau, neurodegeneration). Finally, and most importantly, while each risk factor may have a different mechanism of action on AD biomarkers, "exceptional aging" and protection against AD dementia will come from "net sum" protection against all components of the biomarker cascade.

While important strides have been made in identifying risk factors for AD dementia incidence, further efforts are needed to translate these into effective preventive strategies. Using biomarker studies for understanding the mechanism of action, effect size estimation, selection of appropriate end-points, and better subject recruitment based on subpopulation effects are fundamental for better design and success of prevention trials.

Link: https://doi.org/10.1186/s13195-018-0373-z


IMO it is envirornmental and lifestyle exposure and likely caused by prions.

Interesting to me that Finland has the worst rate per capita and has rougly 150 times the rate versus Singapore.

Also, it is curious that Switzerland has twice the rate as Germany and triple the rate of Austria. It doesn't seem likely to be genetic.


Posted by: Lee at June 6th, 2018 6:25 AM

The current thinking in ALS research, which also involves protein aggregates, is that the large, insoluble aggregates are not particularly harmful. What causes the problem, it turns out, are the smaller, soluble aggregates of just a couple of misfolded peptide chains.

I don't know if there's something similar at work here, but maybe the aggregates that we can see aren't the real problem.

Lee: There's definitely a genetic component to solubility. Different apoE alleles confer radically different levels of risk. This doesn't preclude environmental factors, of course, but I wouldn't rule out genetics as explaining much of the difference between countries.

Posted by: Brandon Berg at June 6th, 2018 7:32 AM

The last paragraph of my last comment should start with, "There's definitely a genetic component to susceptibility."

Posted by: Brandon Berg at June 6th, 2018 7:33 AM

There's also the hygiene hypothesis to consider:

Hygiene and the world distribution of Alzheimer's disease
Epidemiological evidence for a relationship between microbial environment and age-adjusted disease burden

Posted by: CD at June 6th, 2018 8:20 AM

@Lee the difference looks to be due to coding most likely. Singapore is just counting all those deaths as pneumonia, the proximate cause, instead of the underlying cause, like Alzheimer's, which is what Finland is doing.

Posted by: ale at June 6th, 2018 8:24 AM

All I know is that we had better tackle it and tackle it SOON.


Part of Medicare goes bust in 2026 "Medicare Part A, helps pay for hospital, home health services following hospital stays, skilled nursing facility, and hospice care for the aged and disabled."

The rest of it tanks in 2036.

Social Security goes bust in 2034.

Alzheimer's and dementia will account for a large part of this.

This isn't a prediction from some private think tank either. Its from the horses mouth, the Social Security and Medicare Boards of Trustees.


Regenerative medicine is going to have to take a front and center place among policy makers NOW or, well.. by the time most of us get to the point where we need these things... we not only won't have them, but death may look like a pretty good alternative compared to the suffering we will have to endure.

Isn't that sad given our technological capability and raw need?

We have the tools, the people and an all out humanitarian crisis of INSANE proportions, and what is coming out of policy makers? "RUSSIA, RUSSIA, RUSSIA!", "Taking a knee", and other inane pablum being force fed to us by the MSM.

How do we lead the way and make a better world?

Posted by: Mark Borbely at June 6th, 2018 10:40 AM

@Mark B.
I agree, Alzheimer's is a serious problem. I recently joined AARP {I just turned 50, ughh...). AARP is the biggest lobby group for older Americans. I think it would be productive for people prominent in the life extension community make connections with the AARP leadership.

Posted by: CD at June 6th, 2018 11:10 AM


>... but death may look like a pretty good alternative compared to the suffering we will have to endure.

Well, if i have dementia I will probably not realize I am suffering. Everybody else around me, on the other hand could be suffering :)

Posted by: cuberat at June 6th, 2018 11:27 AM


Oh.. they know... they know..at least at first. I'm lucky and my blood relatives seem fairly resistant to it, however... I've been around enough dementia patients to know that they know SOMETHING is wrong. Especially at the early stages of it.

And sadly, its terrifying to endure, both as the sufferer and the caregiver.

Posted by: Mark Borbely at June 6th, 2018 11:59 AM

Alzheimer's seems transmissible to me.

"A subject whose spouse experienced incident dementia onset had a six times greater risk for incident dementia as subjects whose spouses were dementia free (hazard rate ratio (HRR)=6.0, 95% confidence interval (CI)=2.2-16.2, P<.001). In sex-specific analyses, husbands had higher risks (HRR=11.9, 95% CI=1.7-85.5, P=.01) than wives (HRR=3.7, 95% CI=1.2-11.6, P=.03)."


Posted by: Lee at June 6th, 2018 1:03 PM

"Researchers at the Human Microbiology Institute (HMI) have uncovered a potential new Alzheimer's treatment that significantly reversed the late-stage effects of the debilitating neurodegenerative disease.

The results, published in the Journal of Medical Case Reports, details the promising results that the research duo of Victor and George Tetz had in treating a 77-year-old Alzheimer's patient with the repurposed medication deoxyribonuclease I, an enzyme approved by the U.S. Food and Drug Administration for the treatment of mucus buildup in cystic fibrosis patients."


Posted by: Lee at June 6th, 2018 1:07 PM

Etheresia Pretorius at the University of Pretoria in South Africa has published extensive research showing dementia is strongly linked to the formation of fibrin micro clots in the brain, induced by iron overload. Efforts to provide acetycholina have been met with failure. Efforts to address cholesterol and beta amyloid have not been successful either. Resveratrol is a molecule that facilitates cholesterol and beta amyloid efflux (disposal) from the brain. Dr. Pretorius explains her FIBRIN CLOT origin of vascular disease in Current Neurovascular Research 2013 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763776/pdf/CNR-10-269.pdf
The iron induced fibrin clot theory of Alzheimer's disease was presented in Frontiers of Human Neuroscience in 2013 and identifies magnesium as an antidote. https://www.ncbi.nlm.nih.gov/pubmed/24194714 Supplemental iron was demonstrated by Pretorius and colleagues as cause of thrombosis. International Journal Molecule Medicine 2014 https://www.ncbi.nlm.nih.gov/pubmed/24337469

Posted by: Bill Sardi at June 10th, 2018 6:58 AM

I find it interesting to observe the differences in approach to end of life issues. My immediate family recently had a graveyard "visit" where we all sat around...talked a lot...put some decorations on the markers...prayed. My brothers/sisters have taken to hugging a lot...and they can talk until you can't stand it.

My approach is to try and watch my diet...take some supplements/exercise and so forth. Pay attention to the research. Not too much into "magical thinking". Though I try to be a positive thinker. They know I take supplements and so forth but have no interest in the subjects. I'll continue to keep them under observation. LOL. Pretty sure there is no changing them.

Posted by: bob at June 14th, 2018 6:50 AM

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