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Alzheimer disease-associated cystatin C variant undergoes impaired secretion


Benussi, L; Ghidoni, R; Steinhoff, T; Alberici, A; Villa, A; Mazzoli, F; Nicosia, F; Barbiero, L; Broglio, L; Feudatari, E; Signorini, S; Finckh, U; Nitsch, R M; Binetti, G (2003). Alzheimer disease-associated cystatin C variant undergoes impaired secretion. Neurobiology of Disease, 13(1):15-21.

Abstract

CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.

CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2003
Deposited On:08 Sep 2011 06:45
Last Modified:16 Aug 2016 10:15
Publisher:Elsevier
ISSN:0969-9961
Publisher DOI:10.1016/S0969-9961(03)00012-3
PubMed ID:12758063

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