[alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients.
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?


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.
Colciaghi
Francesca
F
Centre of Excellence on Neurodegenerative Diseases and Department of Pharmacolgical Sciences, University of Milano, School of Pharmacy, Italy.
Borroni
Barbara
B
Pastorino
Lucia
L
Marcello
Elena
E
Zimmermann
Martina
M
Cattabeni
Flaminio
F
Padovani
Alessandro
A
Di Luca
Monica
M
D051722:ADAM Proteins; D000072197:ADAM10 Protein; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000097:blood* / Q000134:cerebrospinal fluid*; D001792:Blood Platelets / Q000737:chemistry; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008565:Membrane Proteins / Q000032:analysis / Q000097:blood* / Q000134:cerebrospinal fluid*; D008666:Metalloendopeptidases / Q000032:analysis / Q000097:blood* / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood* / Q000134:cerebrospinal fluid*; D015539:Platelet Activation; D011233:Precipitin Tests
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D010446:Peptide Fragments; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human