Universität zu Köln

Bajaj, Thomas, Ramirez, Alfredo ORCID: 0000-0003-4991-763X and Wagner-Thelen, Holger (2018). Genetics of Alzheimer's disease. Med. Genet., 30 (2). S. 259 - 267. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1863-5490

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Abstract

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia. In contrast to monogenic and early-manifesting forms of AD resulting from highly penetrant mutations in APP, PSEN1, and PSEN2, susceptibility to the sporadic, often late-onset AD (LOAD) is determined by a complex interaction among genetic, epigenetic, and environmental-lifestyle-related factors. Although APOE E > 4 is the strongest genetic risk factor for AD, its effect only accounts for 27.3% of the estimated disease heritability of 58-79%. Through the continuing technical development of genome-wide association studies (GWAS) and next-generation automatic sequencing methods, scientists in large-scale collaborations have succeeded in gradually revealing the missing heritability. Important insights from GWAS and analyses of signaling pathways suggest that microglia, the resident immune cells of the CNS, play a decisive role in the pathogenesis of AD. A considerable number of risk genes identified in genetic studies indicate immune system-related functions and are expressed to a large extent by microglia. Through the description of risk variants in CR1, CLU, SPI1, CD33, MS4A, ABCA7, EPHA1, HLA-DRB5/1, INPP5D, TYROBP, TREM2, PLCG2, and ABI3 the microglia-mediated immune response takes on a central role in the pathogenesis of AD. Of note might be that the PLC gamma 2 variant, p.P522R, exerts a protective effect on LOAD and as an enzyme, PLC gamma 2 offers a classic target for the therapeutic modulation of complex forms of AD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bajaj, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramirez, Alfredo UNSPECIFIED orcid.org/0000-0003-4991-763X UNSPECIFIED Wagner-Thelen, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-183902
DOI:	10.1007/s11825-018-0193-3
Journal or Publication Title:	Med. Genet.
Volume:	30
Number:	2
Page Range:	S. 259 - 267
Date:	2018
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1863-5490
Language:	German
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; COGNITIVE DECLINE; COMMON VARIANTS; CODING VARIANTS; AMYLOID-BETA; A-BETA; TREM2; RISK; CD33 Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18390