Decreased plasma β‐amyloid in the Alzheimer's disease APP A673T variant carriers

    loading  Checking for direct PDF access through Ovid


Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Neuropathology of AD is characterized by accumulation of β‐amyloid (Aβ) peptides generated from amyloid precursor protein (APP).1 Highly penetrant mutations in the APP, PSEN1, and PSEN2 genes cause familial early‐onset AD with autosomal‐dominant inheritance, whereas 25 gene loci have been shown to affect the susceptibility for AD.2 Recent studies have reported rare variants affecting AD risk, such as A673T (rs63750847) in APP,3 and several loss‐of‐function variants in ABCA7.4 A673T variant was detected more often in elderly individuals without AD.3 Mechanistic elucidation suggested that this amino acid change residing adjacent to the proteolytic cleavage site of BACE1, the protease responsible for the production of Aβ, might impair the BACE1 cleavage of APP and thus lead to decreased production of Aβ.3ABCA7 loss‐of‐function variants are enriched in individuals with AD,4 and decreased levels or function of ABCA7 may lead to increased production or impaired clearance of Aβ.7 Here, we analyzed the plasma levels of Aβ40 and Aβ42 in the carriers of rare AD‐related variants APP A673T and ABCA7 rs200538373 with matched controls in a population‐based cohort.

Related Topics

    loading  Loading Related Articles