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

Francesca Colciaghi, Barbara Borroni, Lucia Pastorino, Elena Marcello, Martina Zimmermann, Flaminio Cattabeni, Alessandro Padovani, Monica Di Luca

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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.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalMolecular medicine (Cambridge, Mass.)
Volume8
Issue number2
Publication statusPublished - 2002

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Amyloid Precursor Protein Secretases
Cerebrospinal Fluid
Alzheimer Disease
Blood Platelets
Amyloid beta-Protein Precursor
Western Blotting
Disintegrins
Metalloproteases
Thrombin
Membranes
Antibodies

ASJC Scopus subject areas

  • Genetics

Cite this

Colciaghi, F., Borroni, B., Pastorino, L., Marcello, E., Zimmermann, M., Cattabeni, F., ... Di Luca, M. (2002). α-secretase ADAM10 as well as αAPPs is reduced in platelets and CSF of Alzheimer disease patients. Molecular medicine (Cambridge, Mass.), 8(2), 67-74.

α-secretase ADAM10 as well as αAPPs is reduced in platelets and CSF of Alzheimer disease patients. / Colciaghi, Francesca; Borroni, Barbara; Pastorino, Lucia; Marcello, Elena; Zimmermann, Martina; Cattabeni, Flaminio; Padovani, Alessandro; Di Luca, Monica.

In: Molecular medicine (Cambridge, Mass.), Vol. 8, No. 2, 2002, p. 67-74.

Research output: Contribution to journalArticle

Colciaghi, F, Borroni, B, Pastorino, L, Marcello, E, Zimmermann, M, Cattabeni, F, Padovani, A & Di Luca, M 2002, 'α-secretase ADAM10 as well as αAPPs is reduced in platelets and CSF of Alzheimer disease patients', Molecular medicine (Cambridge, Mass.), vol. 8, no. 2, pp. 67-74.
Colciaghi F, Borroni B, Pastorino L, Marcello E, Zimmermann M, Cattabeni F et al. α-secretase ADAM10 as well as αAPPs is reduced in platelets and CSF of Alzheimer disease patients. Molecular medicine (Cambridge, Mass.). 2002;8(2):67-74.
Colciaghi, Francesca ; Borroni, Barbara ; Pastorino, Lucia ; Marcello, Elena ; Zimmermann, Martina ; Cattabeni, Flaminio ; Padovani, Alessandro ; Di Luca, Monica. / α-secretase ADAM10 as well as αAPPs is reduced in platelets and CSF of Alzheimer disease patients. In: Molecular medicine (Cambridge, Mass.). 2002 ; Vol. 8, No. 2. pp. 67-74.
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AU - Borroni, Barbara

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AU - Marcello, Elena

AU - Zimmermann, Martina

AU - Cattabeni, Flaminio

AU - Padovani, Alessandro

AU - Di Luca, Monica

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N2 - 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.

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