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

被引:209
作者
Colciaghi, F
Borroni, B
Pastorino, L
Marcello, E
Zimmermann, M
Cattabeni, F
Padovani, A
Di Luca, M
机构
[1] Univ Milan, Dept Pharmacol Sci, Sch Pharm, I-20133 Milan, Italy
[2] Univ Milan, Sch Pharm, Ctr Excellence Neurodegerat Dis, I-20133 Milan, Italy
[3] Univ Brescia, Sch Med, Dept Med Sci, Neurol Unit, Brescia, Italy
关键词
D O I
10.1007/BF03402076
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alphaAPPs? 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 (alphaAPPs) 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 alphaAPPs released from platelets. Moreover, in the same pool of AD patients, alphaAPPs 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 alphaAPPs 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.
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页码:67 / 74
页数:8
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