title: Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population.
abstract: 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 β-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 age-at-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 β-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 β-amyloid pathology at the age of 104.8 years supports the concept that the A673T variant protects the brain against β-amyloid pathology and AD.
authors.affiliation: Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
authors.forename: Mia
authors.initials: M
authors.lastname: Kero
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.forename: Tuomo
authors.initials: T
authors.lastname: Polvikoski
authors.forename: Maarit
authors.initials: M
authors.lastname: Tanskanen
authors.forename: Raimo
authors.initials: R
authors.lastname: Sulkava
authors.forename: Lilja
authors.initials: L
authors.lastname: Jansson
authors.forename: Liisa
authors.initials: L
authors.lastname: Myllykangas
authors.forename: Pentti J
authors.initials: PJ
authors.lastname: Tienari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D019579:Neocortex / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor