Fight Aging!

One of the more interesting questions regarding Alzheimer's disease is why it only arises in some of the people with well-known risk factors. Only some people with higher levels of chronic inflammation. Only some frail people. Only some obese people. Only some people with detectable amyloid aggregation in the brain, as noted in the materials here. A plausible explanation, though still quite possibly not the right explanation, is that persistent viral infection is the driving force in Alzheimer's disease. Only a fraction of the population is significantly impacted in this way by varieties of herpesvirus, which seems a better fit than theories of disease progression involving mechanisms that operate in everyone.

Including nearly 20,000 participants, the largest study on amyloid prevalence to date estimates that a third of cognitively normal people older than 70 have amyloid building up in their brains. Compared amyloid prevalence across age, cognitive status, ApoE genotype, and by biomarker modality (i.e., CSF versus PET). A total of 10,139 participants in 50 cohorts had undergone amyloid-PET scans, while 8,958 participants across 51 cohorts had had CSF Aβ42 measured; only 1,571 underwent both.

Among those without dementia, amyloid cropped up in 24 percent of those with normal cognition, 27 percent of people with subjective cognitive decline, and 51 percent of people with mild cognitive impairment. Findings were similar whether amyloid-PET or CSF Aβ42 was used. Amyloid prevalence increased with age among those without dementia. For example, based on the adjusted CSF Aβ42 measurements, 17 percent of cognitively normal people between the ages of 50-54 had evidence of amyloid. By age 70, a third did, and by age 95, more than half did.

The size of this study gave the researchers enough statistical power to compare amyloid prevalence across different ApoE genotypes. E4/E4 carriers started accumulating amyloid at the youngest age, followed by E3/E4, E2/E4, E3/E3, and E2/E3 carriers. Notably, the amyloid prevalence among E3/E4 carriers was 10 percent higher than it was among E2/E4 carriers across all groups without dementia, highlighting a protective effect of the E2 allele.

Link: https://www.alzforum.org/news/research-news/amyloid-lurks-third-cognitively-normal-people-over-70