[alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients (original) (raw)

Abstract

BACKGROUND: Members of membrane-bound disintegrin metalloproteinases (ADAMs) were shown to be capable of cleaving amyloid precursor protein (APP) at the alpha-cleavage site in different cell systems. One of the candidate alpha-secretases identified in this family is ADAM10. The present study addresses the following major questions: 1) Are the levels of an alpha-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 alpha APPs? 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 alpha-secretase metabolite (alpha APPs) 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 alpha APPs released from platelets. Moreover, in the same pool of AD patients, alpha APPs 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 alpha APPs 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.

Full Text

The Full Text of this article is available as a PDF (1,005.0 KB).