Plasma levels of soluble ADAM10 are increased in persons with Alzheimer’s disease and Mild Cognitive Impairment

Abstract

AbstractBackgroundActive ADAM10 is a transmembrane protein with α‐secretase function that inhibits β‐amyloid (Aβ) peptide formation, an important neuropathological agent of Alzheimer’s disease (AD). In addition, persons with cognitive decline, such as Mild Cognitive Impairment (MCI), have a high conversion rate to AD. Previous studies show that the levels of active platelet ADAM10 are reduced in persons with AD dementia, compared with cognitively healthy individuals. In blood plasma the inactive and soluble form of ADAM10 is found. In this study we investigated the levels of inactive ADAM10 in plasma in order to corroborate with previous results found in platelets.MethodThis study was approved by the UFSCar’s Research Ethics Committee (CAAE: 02763012.0.0000.5504). Altogether, samples from 88 participants (n = 28 MCI, n = 31 AD and n = 29 controls) were analysed in this study. Blood samples were collected, plasma was separated and total protein content (15µg) was run on gel electrophoresis (SDS‐PAGE). Soluble ADAM10 (50‐55kDa) was identified by western blotting, using the anti‐ADAM10 antibody (Abcam, Ab39180) followed by the secondary antibody (Abcam, Ab97051). The serum albumin protein (66kDa) and a “young control” performed with plasma samples from a young donnor were used as endogen controls to avoid interassay biases in the densitometry analyses. Bands were measured by volume adjusted in Image Lab software and statistical analysis were performed in GraphPad Prism software.ResultPlasma levels of soluble ADAM10 are increased in persons with MCI (p = 0.0325) and AD (p = 0.0129), compared with cognitively healthy older adults.ConclusionPlasma‐soluble ADAM10 has potential as a biomarker molecule for AD. Analyses in plasma are advantageous as they represent an easily accessible and low‐cost tool that can be used in the future by health services to aid in the early diagnosis of AD.