Rates of β-amyloid deposition indicate widespread simultaneous accumulation throughout the brain

Abstract

Amyloid plaque aggregation is a pathologic hallmark of Alzheimer's disease (AD) that occurs early in the disease. However, little is known about its progression throughout the brain. Using Pittsburgh Compound B (PIB)-PET imaging, we investigated the progression of regional amyloid accumulation in cognitively normal older adults. We found that all examined regions reached their peak accumulation rates 24–28 years after an estimated initiation corresponding to the mean baseline PIB-PET signal in amyloid-negative older adults. We also investigated the effect of increased genetic risk conferred by the apolipoprotein-E ɛ4 allele on rates of amyloid accumulation, as well as the relationship between regional amyloid accumulation and regional tau pathology, another hallmark of AD, measured with Flortaucipir-PET. Carriers of the ɛ4 allele had faster amyloid accumulation in all brain regions. Furthermore, in all regions excluding the temporal lobe, faster amyloid accumulation was associated with greater tau burden. These results indicate that amyloid accumulates near-simultaneously throughout the brain and is associated with higher AD pathology, and that genetic risk of AD is associated with faster amyloid accumulation.