Platelet APP levels from subjects with Alzheimer’s disease and mild cognitive impairment

Authors: Augusto Magno, Jessyka Maria de França Bram, Leda Leme Talib, Helena Passarelli Giroud Joaquim, Wagner Farid Gattaz, Orestes Vicente Forlenza

Published: 2020-12-07

DOI: 10.1002/alz.043436

Source: Full article


Abstract

AbstractBackgroundThe clinical diagnosis of Alzheimer’s disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process as Mild Cognitive Impairment (MCI). Beta‐amyloid peptide (Aβ) accumulation is one of the hallmarks of AD. It is well‐known that the main mechanism of Aβ production, whose accumulation is one of the hallmarks of AD, is from abnormalities in amyloid‐beta precursor protein (APP) metabolism. APP is an integral transmembrane protein widely expressed in neuronal and peripheral tissues and the enzymatic machinery needed to process APP in neurons is also present in platelets. The aim of the present study was to compare the protein level of APP to discriminate cases of AD and MCI from controls.MethodThe APP protein levels were measured in platelets from non‐medicated older adults with AD (n=10), MCI (n=17) and healthy elders (n=12) by western blotting. The densitometries of 130kDa and 110kDa were used to estimate the levels of APP and APP–ratio. Each sample was analyzed in duplicate and for normalization of platelet assay values we used β‐actin as loading (internal) control. All statistical analyses were performed with the aid of the software Statistical Package for the Social Sciences (SPSS) ‐ version 14. Differences in sociodemographic characteristics and platelets APP concentrations at baseline were analyzed using the Kruskal‐Wallis.ResultThere was no difference regarding gender distribution or age among the three groups (p=0.310 and p=0.088, respectively). We found a down expression of 110kDa‐APP‐fragment in AD compared to MCI and controls. In contrast, there was no difference nor in 130kDa‐APP‐fragment (p=0.212) either APPratio (p=0.736).ConclusionOur findings indicate that 110kDa‐APP‐fragment is down regulated in AD and may be a marker of altered APP metabolism in platelets since MCI state when compared to controls.