Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles.

Abstract

Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III-VI) stages, which characterize NFTs' accumulation. We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (APOE) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP). Resistance, characterized by low (0-II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III-VI) Braak stages, increased significantly with age in both men and women for each APOE allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the APOE allele. The identification of factors underlying resistance and resilience against AD-related pathologies is essential for promoting cognitively healthy aging. We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD).This study included individuals who were not diagnosed with AD.Braak stages 0-II and III-VI were considered as a measure of resistance and resilience, respectively.Resistance was stronger at ages younger than 85 years in non-carriers of the apolipoprotein E (APOE) ε4 allele.Resilience increased with age for each APOE allele independently of sex.At age 85 years and older, high resilience(>50%) was observed in women regardless of the APOE allele.