The genetics of Alzheimer's disease.

被引：48

作者：

Schellenberg G.D. ^{[1
]}

D'Souza I. ^{[1
]}

Poorkaj P. ^{[1
]}

机构：

[1] Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Avenue, Seattle

来源：

Current Psychiatry Reports | 2000年 / 2卷 / 2期

关键词：

Alzheimer Disease; ApoE Genotype; Amyloid Precursor Protein Mutation; Entorhinal Cortex Lesion;

D O I：

10.1007/s11920-000-0061-z

中图分类号：

学科分类号：

摘要：

Alzheimer's disease (AD) is a genetically complex disorder. Mutations in the amyloid precursor protein and presenilin 1 (PS1) genes are fully penetrant and cause early-onset AD. Mutations in presenilin 2, a PS1 homologue, cause partially penetrant autosomal dominant AD with onset age beginning at 40 years and extending past 75 years. A fourth gene, apolipoprotein E (ApoE) is a risk-factor for late-onset AD. Over 40 genes have been tested as AD candidate genes, yet none has been clearly established as an AD risk factor. Linkage studies have implicated a number of chromosome regions as possible sites for late-onset AD loci with the strongest evidence being for chromosome 12. Candidate genes in this region include alpha2-macroglobulin (A2M) and low-density lipoprotein receptor-related gene (LRP), although neither has been clearly established as an AD gene. Identification of additional late-onset genes will require larger samples, more sophisticated analysis methods, and large-scale positional cloning efforts.

引用

页码：158 / 164

页数：6

共 162 条

[1]

Alvarez V(1999)Association between an alpha(2) macroglobulin DNA polymorphism and late-onset Alzheimer’s disease Biochem Biophys Res Comm 264 48-50

[2]

Alvarez R(1998)Low density lipoprotein receptor related protein gene exon 3 polymorphism association with Alzheimer’s disease in Chinese Neurosci Lett 247 33-36

[3]

Lahoz CH(1999)The polymorphism in exon 3 of the low density lipoprotein receptor-related protein gene is weakly associated with Alzheimer’s disease Neurosci Lett 259 29-32

[4]

Baum L(1997)The role of heredity in late-onset Alzheimer disease and vascular dementia - A twin study Arch Gen Psych 54 264-270

[5]

Chen L(1998)Alpha-2 macroglobulin is genetically associated with Alzheimer disease Nat Genet 19 357-360

[6]

Ng HK(1998)A polymorphism in the regulatory region of APOE associated with risk for Alzheimer’s dementia Nat Genet 18 69-71

[7]

Beffert U(1999)Apolipoprotein E promoter and alpha 2-macroglobulin polymorphisms are not genetically associated with Chinese late onset Alzheimer’s disease Neurosci Lett 269 173-177

[8]

Arguin C(1997)Lack of association of a polymorphism in the low-density lipoprotein receptor-related protein gene with Alzheimer disease Arch Neurol 54 1289-1292

[9]

Poirier J(1994)Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease Nat Genet 7 180-184

[10]

Bergem ALM(1993)Gene Dose of Apolipoprotein-E Type-4 Allele and the Risk of Alzheimer’s Disease in Late Onset Families Science 261 921-923

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