Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Dr Tuomo Polvikoski

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.


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

URL: http://dx.doi.org/10.1016/j.neurobiolaging.2012.09.017

DOI: 10.1016/j.neurobiolaging.2012.09.017


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share