Abstract |
The APP717 mutations discovered in only a few early onset Alzheimer's disease (AD) families have confirmed the genetic heterogeneity of this disorder. To identify the other gene(s) involved in the disease we selected the protease inhibitor, Cystatin-C, as a candidate gene. Cystatin-C is an amyloidogenic protein causing hereditary cerebral haemorrhage with amyloidosis-Icelandic type ( HCHWA-I). It is localised with the beta-amyloid peptide in the arterial walls of AD brains. We have analysed the segregation of a polymorphic marker in this gene in 8 early onset AD families. Two early onset families showed clear non-segregation of the marker with the disease. When the 8 families are analysed together (assuming only one other gene is involved), they present exclusion linkage criteria. These data indicate that Cystatin-C is not the site of the defect in 2 families and is not likely to be in the other families analysed. We conclude that the deposition of Cystatin-C in AD is a secondary event in the disease process, and that this gene is not pathogenic in familial AD.
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Authors | M Parfitt, R Crook, P Roques, M Rossor, M C Chartier-Harlin |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 154
Issue 1-2
Pg. 81-3
(May 14 1993)
ISSN: 0304-3940 [Print] Ireland |
PMID | 8361651
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- CST3 protein, human
- Cerebrospinal Fluid Proteins
- Cystatin C
- Cystatins
- Genetic Markers
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Topics |
- Adult
- Aged
- Alzheimer Disease
(genetics, metabolism)
- Amyloid beta-Peptides
(metabolism)
- Cerebrospinal Fluid Proteins
(genetics, metabolism)
- Cystatin C
- Cystatins
(genetics)
- Genetic Linkage
- Genetic Markers
- Humans
- Middle Aged
- Polymerase Chain Reaction
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