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

Lookup NU author(s): Dr Tuomo Polvikoski


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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.

Publication metadata

Author(s): Kero M, Paetau A, Polvikoski T, Tanskanen M, Sulkava R, Jansson L, Myllykangas L, Tienari PJ

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2013

Volume: 34

Issue: 5

Pages: 1518.e1-1518.e3

Print publication date: 24/10/2012

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier


DOI: 10.1016/j.neurobiolaging.2012.09.017


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