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

INTRODUCTION

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.

METHODS

We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E () alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).

RESULTS

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 allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the allele.

DISCUSSION

The identification of factors underlying resistance and resilience against AD-related pathologies is essential for promoting cognitively healthy aging.

HIGHLIGHTS

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 () ε4 allele.Resilience increased with age for each allele independently of sex.At age 85 years and older, high resilience (>50%) was observed in women regardless of the allele.