期刊
NEUROBIOLOGY OF AGING
卷 31, 期 5, 页码 725-731出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2008.06.012
关键词
Early-onset Alzheimer's disease; Presenilins; APP; Mutations
资金
- Intramural Research Program of NIA [1 Z01 AG000950-06 2007]
- Canadian Institutes of Health Research
- Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/27442/2006, SFRH/BD/29647/2006]
- MRC [G0701075] Funding Source: UKRI
- Alzheimers Research UK [ART-PG2010-1] Funding Source: researchfish
- Medical Research Council [G0701075] Funding Source: researchfish
- NATIONAL INSTITUTE ON AGING [ZIAAG000950, Z01AG000951] Funding Source: NIH RePORTER
Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer's disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early-onset AD (mean age at onset of 52.9 years; range 31-64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d'Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new non-synonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations. (C) 2008 Elsevier Inc. All rights reserved.
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