α-secretase ADAM10 as well as αAPPs is reduced in platelets and CSF of Alzheimer disease patients

Abstract

Background: Members of membrane-bound disintegrin metalloproteinases (ADAMs) were shown to be capable of cleaving amyloid precursor protein (APP) at the α-cleavage site in different cell systems. One of the candidate α-secretases identified in this family is ADAM10. The present study addresses the following major questions: 1) Are the levels of an α-secretase candidate (i.e., ADAM10) reduced in accessible cells of Alzheimer Disease (AD) patients? 2) Are ADAM10 levels in the peripheral cells of AD patients related to a concomitant decrease in αAPPs? Materials and Methods: Western Blot analysis of ADAM10 is performed on platelet homogenates from 33 sporadic AD patients and on 26 age-matched control subjects. Moreover, the levels of α-secretase metabolite (αAPPs) are tested both in platelets and cerebrospinal fluid (CSF) of the same pool of subjects by means of Western blot with a specific antibody. Results: A significant decrease of platelet ADAM10 levels is observed in patients affected by probable AD when compared to control subjects and this is paralleled by a reduced level of αAPPs released from platelets. Moreover, in the same pool of AD patients, αAPPs levels were reduced concomitantly in CSF. Conclusions: ADAM10 is expressed in platelets. A reduced level of ADAM10 is observed in platelets obtained from AD patients compared to age-matched controls. Further, in the same pool of AD patients, a qualitatively and quantitatively similar decrease in αAPPs is present both in thrombin-activated platelets and CSF, thus suggesting that alterations of APP processing might occur both in the neuronal compartment and peripheral cells.