However, that concern is somewhat mitigated by evidence documenting the presence of Aβ plaques in cognitively unimpaired normal adults45,46, that plasma Aβ42 is significantly decreased in individuals with mild cognitive impairment and Alzheimer’s disease patients compared to age-matched controls38, and that tau pathology is more strongly associated with cognitive decline than Aβ19. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.