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ApoE4 reaches elevated amyloid 15 yrs before non-ApoE4

Posted: Sat Jun 13, 2020 8:09 am
by NF52
The role of toxic forms of amyloid in risk of Alzheimer's is still unclear. Yet it is clearly visible on PET scans 10-20 years before clinical tests and widespread neuronal damage result in a diagnosis of Alzheimer's. So it is now viewed as a "biomarker" of "preclinical Alzheimer's disease". Similar to coronary plaque on a coronary calcium scan, elevated amyloid can indicate a disease process without indicating either an imminent or certain risk of severe disease.

The long-term Alzheimer's Disease Neuroimaging Initiative (ADNI) and A4 Study screened and followed people with and without elevated amyloid for years. This is from a peer-reviewed pre-print article: Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition
APOE-ε4 carriers reached abnormal levels of Aβ ∼15 years earlier than non-carriers. The APOE-ε4 carriers reached abnormal levels earlier at age 63 (59.6-70.3), however, non-carriers reached the threshold later at age 78(76.1-84.4)....
APOE-ε4 carriers and non-carriers had no differences in Aβ deposition rates beyond the threshold
These results suggest that primary and secondary prevention trials, looking to recruit at the earliest stages of disease, should target APOE-ε4 carriers between the ages of 60 and 66 and non-carriers between the ages of 76 and 84.
A talk by Dr. Reisa Sperling yesterday titled “Can We Predict and Treat Alzheimer’s Disease a Decade before Dementia? (and Why We Must!)” focuses strongly on the risk to women with ApoE 4 of having elevated amyloid levels by the mid-60's, and notes that women would have started to be amyloid positive (but not yet elevated) at age 55.

None of the lifestyle factors we associate with continued cognitive health changed the risk of elevated amyloid , even those likely to be protective against cognitive decline. As Dr. Sperling said "Amyloid beta appears to be driven by genetics." The recording will be available soon here: https://sites.brown.edu/ideari/watch-the-livestream/. I'll update the link when it becomes available; the slides are fascinating!

Here some good parting news from Dr. Sperling:
1. Low vascular risk protects people from development of tau and from cognitive decline for at least 6 years even with elevated amyloid
2. People who walked 8900 steps a day were resilient to the effects of elevated amyloid: Associations of Physical Activity and β-Amyloid With Longitudinal Cognition and Neurodegeneration in Clinically Normal Older Adults
Greater physical activity and lower vascular risk independently attenuated the negative association of Aβ burden with cognitive decline and neurodegeneration in asymptomatic individuals. These findings suggest that engaging in physical activity and lowering vascular risk may have additive protective effects on delaying the progression of Alzheimer disease.
Dr. Sperling notes that people with ApoE 4 are likely to need an "all of the above" array of prevention strategies, which is very similar to what I remember reading at the end of Dr. Bredesen's book. As we used to say when working with kids with traumatic brain injuries, we need to use the "whatever it takes" approach.