Article

The Genetics of Alzheimer Disease: Current Status and Future Prospects

Harvard University, Cambridge, Massachusetts, United States
JAMA Neurology (Impact Factor: 7.42). 03/1998; 55(3):294-6. DOI: 10.1001/archneur.55.3.294
Source: PubMed

ABSTRACT

Four genes involved in the development of Alzheimer disease have been identified. Three fully penetrant (deterministic) genes lead to the development of Alzheimer disease in patients younger than 60 years: the amyloid beta-protein precursor on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1. Together, they account for about half of this early-onset form of the disease. One genetic risk factor--apolipoprotein E-4--is associated with late-onset Alzheimer disease. It accounts for a substantial fraction of disease burden but seems to act primarily to lower the age of disease onset. In general, none of these genes can be easily adapted for use as a diagnostic or predictive test for Alzheimer disease. Research activity includes searching for additional genes, especially for late-onset disease, and elucidating the mechanism of action of all identified genes as part of a long-term effort to develop more effective therapeutic and preventive strategies.

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    • "Less common mutations are found in the gene for valosin-containing protein (VCP) on 9p21-12 [18], in the gene coding for TDP-43 [19], in the gene for charged multivesicular binding protein 2B (CHMP2B) [20], and in the fused-in-sarcoma (FUS) gene on chromosome 16 [21], but there still remain cases with as yet unidentified genetic defects. Regarding age of onset of FTD, FUS gene mutations have been associated with age of onset ≤40 years of age [21]; on the other hand, early onset cases of alzheimer disease (AD) have been reported to be associated with mutations in the genes encoding for presenilin 1 (PS1) on chromosome 14, presenilin 2 (PS2) on chromosome 1, and the amyloid βprotein precursor (APP) on chromosome 21 [13]. FTD in a remarkably young patient has to be diagnosed with caution. "
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    Full-text · Article · Jul 2015 · Clinical neuropharmacology
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    • "Less common mutations are found in the gene for valosin-containing protein (VCP) on 9p21-12 [18], in the gene coding for TDP-43 [19], in the gene for charged multivesicular binding protein 2B (CHMP2B) [20], and in the fused-in-sarcoma (FUS) gene on chromosome 16 [21], but there still remain cases with as yet unidentified genetic defects. Regarding age of onset of FTD, FUS gene mutations have been associated with age of onset ≤40 years of age [21]; on the other hand, early onset cases of alzheimer disease (AD) have been reported to be associated with mutations in the genes encoding for presenilin 1 (PS1) on chromosome 14, presenilin 2 (PS2) on chromosome 1, and the amyloid βprotein precursor (APP) on chromosome 21 [13]. FTD in a remarkably young patient has to be diagnosed with caution. "
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    Full-text · Article · Mar 2015 · European Psychiatry
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