Abstract
ObjectiveApolipoprotein E (APOE) ε2 carriers may be protected from dementia because of reduced levels of cortical β-amyloid. In the oldest-old, however, APOE ε2 carriers have high β-amyloid plaque scores and preserved cognition. We compared different measures of β-amyloid pathology across APOE genotypes in the oldest-old, and their relationship with dementia. MethodsThe study included 96 participants from The 90+ Study. Using all information, dementia diagnoses were made. Neuropathological examination included staging for amyloid plaques and β-amyloid cortical percent area stained by NAB228 antibody. ResultsBoth APOE ε2 and APOE ε4 carriers had high Consortium to Establish a Registry for Alzheimer’s Disease plaque scores. However, APOE ε2 carriers had low cortical β-amyloid percent areas. β-amyloid percent area was associated with dementia across APOE genotypes. ConclusionsLower levels of percent area in APOE ε2 carriers may reflect lower total β-amyloid and may contribute to APOE ε2 carriers’ decreased risk of dementia, despite high β-amyloid plaque scores. The relationship between β-amyloid plaques and dementia in the oldest-old may vary by APOE genotype.
Highlights
Alzheimer's disease (AD) affects more than 5 million people in the United States alone, at far-reaching social and financial costs
In this study of the oldest-old, we found that β-amyloid percent area but not CERAD plaque score was associated with dementia in all three apolipoprotein E (APOE) genotypes
These findings may help explain the surprising dissociation between AD neuropathology and dementia that we previously found in APOE ε2 carriers in this cohort [16]
Summary
Alzheimer's disease (AD) affects more than 5 million people in the United States alone, at far-reaching social and financial costs. The incidence of dementia (mostly AD) continues to increase with age and is more than 18%/year in people age 90 years and older (the oldest-old) [1]. The relationship between clinical AD and the hallmark pathology of AD, β-amyloid plaques, is well established in the younger elderly (age, 65–90 years) [2]. This relationship is still equivocal in the oldest-old. Several studies have suggested that β-amyloid plaques are not associated with dementia [3,4], whereas others have found that this relationship continues into the oldest-old [5,6]. Based on the recent attention to βamyloid-based biomarkers, it will become increasingly important to understand this relationship in the oldest-old, the fastest growing age group in the country
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