Genetic insights in Alzheimer's disease

被引：274

作者：

Bettens, Karolien ^{[1
,2
]}

Sleegers, Kristel ^{[1
,2
]}

Van Broeckhoven, Christine ^{[1
,2
]}

机构：

[1] Univ Antwerp, VIB Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2610 Antwerp, Belgium

[2] Univ Antwerp, Inst Born Bunge, B-2610 Antwerp, Belgium

来源：

LANCET NEUROLOGY | 2013年 / 12卷 / 01期

关键词：

GENOME-WIDE ASSOCIATION; COMPLEMENT RECEPTOR 1; APP LOCUS DUPLICATION; COPY NUMBER VARIATION; COMMON VARIANTS; PLASMA CLUSTERIN; MISSING HERITABILITY; CEREBROSPINAL-FLUID; IDENTIFIES VARIANTS; MISSENSE MUTATIONS;

D O I：

10.1016/S1474-4422(12)70259-4

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). The identification of new susceptibility genes has opened new avenues for exploration of the underlying disease mechanisms. In addition to detecting novel risk factors in large samples, next-generation sequencing approaches can deliver novel insights with even small numbers of patients. The shift in focus towards translational studies and sequencing of individual patients places each patient's biomaterials as the central unit of genetic studies. The notional shift needed to make the patient central to genetic studies will necessitate strong collaboration and input from clinical neurologists.

引用

页码：92 / 104

页数：13

共 129 条

[1] Novel late-onset Alzheimer disease loci variants associate with brain gene expression [J].

Allen, Mariet ;

Zou, Fanggeng ;

Chai, High Seng ;

Younkin, Curtis S. ;

Crook, Julia ;

Pankratz, V. Shane ;

Carrasquillo, Minerva M. ;

Rowley, Christopher N. ;

Nair, Asha A. ;

Middha, Sumit ;

Maharjan, Sooraj ;

Thuy Nguyen ;

Ma, Li ;

Malphrus, Kimberly G. ;

Palusak, Ryan ;

Lincoln, Sarah ;

Bisceglio, Gina ;

Georgescu, Constantin ;

Schultz, Debra ;

Rakhshan, Fariborz ;

Kolbert, Christopher P. ;

Jen, Jin ;

Haines, Jonathan L. ;

Mayeux, Richard ;

Pericak-Vance, Margaret A. ;

Farrer, Lindsay A. ;

Schellenberg, Gerard D. ;

Petersen, Ronald C. ;

Graff-Radford, Neill R. ;

Dickson, Dennis W. ;

Younkin, Steven G. ;

Ertekin-Taner, Niluefer .

NEUROLOGY, 2012, 79 (03) :221-228

[2]

Alzheimer's Disease International Consortium, WORLD ALZHEIMER REPO

[3] The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease [J].

Antunez, Carmen ;

Boada, Merce ;

Gonzalez-Perez, Antonio ;

Gayan, Javier ;

Ramirez-Lorca, Reposo ;

Marin, Juan ;

Hernandez, Isabel ;

Moreno-Rey, Concha ;

Jesus Moron, Francisco ;

Lopez-Arrieta, Jesus ;

Mauleon, Ana ;

Rosende-Roca, Maitee ;

Noguera-Perea, Fuensanta ;

Legaz-Garcia, Agustina ;

Vivancos-Moreau, Laura ;

Velasco, Juan ;

Miguel Carrasco, Jose ;

Alegret, Montserrat ;

Antequera-Torres, Martirio ;

Manzanares, Salvadora ;

Romo, Alejandro ;

Blanca, Irene ;

Ruiz, Susana ;

Espinosa, Anna ;

Castano, Sandra ;

Garcia, Blanca ;

Martinez-Herrada, Begona ;

Vinyes, Georgina ;

Lafuente, Asuncion ;

Becker, James T. ;

Jorge Galan, Jose ;

Serrano-Rios, Manuel ;

Vazquez, Enrique ;

Tarraga, Lluis ;

Eugenia Saez, Maria ;

Lopez, Oscar L. ;

Miguel Real, Luis ;

Ruiz, Agustin .

GENOME MEDICINE, 2011, 3

[4] Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory [J].

Barral, S. ;

Bird, T. ;

Goate, A. ;

Farlow, M. R. ;

Diaz-Arrastia, R. ;

Bennett, D. A. ;

Graff-Radford, N. ;

Boeve, B. F. ;

Sweet, R. A. ;

Stern, Y. ;

Wilson, R. S. ;

Foroud, T. ;

Ott, J. ;

Mayeux, R. .

NEUROLOGY, 2012, 78 (19) :1464-1471

[5] Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease [J].

Bateman, Randall J. ;

Xiong, Chengjie ;

Benzinger, Tammie L. S. ;

Fagan, Anne M. ;

Goate, Alison ;

Fox, Nick C. ;

Marcus, Daniel S. ;

Cairns, Nigel J. ;

Xie, Xianyun ;

Blazey, Tyler M. ;

Holtzman, David M. ;

Santacruz, Anna ;

Buckles, Virginia ;

Oliver, Angela ;

Moulder, Krista ;

Aisen, Paul S. ;

Ghetti, Bernardino ;

Klunk, William E. ;

McDade, Eric ;

Martins, Ralph N. ;

Masters, Colin L. ;

Mayeux, Richard ;

Ringman, John M. ;

Rossor, Martin N. ;

Schofield, Peter R. ;

Sperling, Reisa A. ;

Salloway, Stephen ;

Morris, John C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (09) :795-804

[6] Presenilin clinical mutations can affect γ-secretase activity by different mechanisms [J].

Bentahir, M ;

Nyabi, O ;

Verhamme, J ;

Tolia, A ;

Horré, K ;

Wiltfang, J ;

Esselmann, H ;

De Strooper, B .

JOURNAL OF NEUROCHEMISTRY, 2006, 96 (03) :732-742

[7] SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population [J].

Bettens, Karolien ;

Brouwers, Nathalie ;

Engelborghs, Sebastiaan ;

De Deyn, Peter P. ;

Van Broeckhoven, Christine ;

Sleegers, Kristel .

HUMAN MUTATION, 2008, 29 (05) :769-770

[8] Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk [J].

Bettens, Karolien ;

Brouwers, Nathalie ;

Engelborghs, Sebastiaan ;

Lambert, Jean-Charles ;

Rogaeva, Ekaterina ;

Vandenberghe, Rik ;

Le Bastard, Nathalie ;

Pasquier, Florence ;

Vermeulen, Steven ;

Van Dongen, Jasper ;

Mattheijssens, Maria ;

Peeters, Karin ;

Mayeux, Richard ;

St George-Hyslop, Peter ;

Amouyel, Philippe ;

De Deyn, Peter P. ;

Sleegers, Kristel ;

Van Broeckhoven, Christine .

MOLECULAR NEURODEGENERATION, 2012, 7

[9]

Bickeboller H, 1997, AM J HUM GENET, V60, P439

[10] Genetic Variation and Neuroimaging Measures in Alzheimer Disease [J].

Biffi, Alessandro ;

Anderson, Christopher D. ;

Desikan, Rahul S. ;

Sabuncu, Mert ;

Cortellini, Lynelle ;

Schmansky, Nick ;

Salat, David ;

Rosand, Jonathan .

ARCHIVES OF NEUROLOGY, 2010, 67 (06) :677-685

← 1 2 3 4 5 6 7 8 9 10 →