Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population (original) (raw)

2013, Neurobiology of Aging

Pathogenic mutations of the APP gene, leading to early-onset Alzheimer's disease (AD) have been known for more than 20 years. Recently, it was discovered that APP mutations might also be protective. A rare variant A673T reportedly protects against AD and age-related cognitive impairment and might functionally inhibit proteolytic cleavage at the b-secretase site of APP. We sequenced APP exon 16 in a population-based sample of 515 Finnish subjects aged 85 or older. Neuropathologic data were available in 274. We found the A673T variant in 1 subject (0.2%), who lived until age 104.8 years (second highest ageat-death in the cohort). Neuropathologic analysis showed little beta-amyloid pathology (Consortium to Establish a Registry for Alzheimer's Disease score 0). Some vascular amyloid was detected in meningeal arteries suggesting that vascular b-amyloid accumulation might be less inhibited than the parenchymal. She was demented at the age of 104, most likely because of hippocampal sclerosis. The low amount of parenchymal b-amyloid pathology at the age of 104.8 years supports the concept that the A673T variant protects the brain against b-amyloid pathology and AD.