Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
- J. Lambert, C. Ibrahim-Verbaas, P. Amouyel
- BiologyNature Genetics
- 27 October 2013
In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
- B. Kunkle, B. Grenier‐Boley, M. Pericak-Vance
- BiologyNature Genetics
- 28 February 2019
A large genome-wide association meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.
Analysis of shared heritability in common disorders of the brain
- V. Anttila, B. Bulik-Sullivan, B. Crespo-Facorro
- Psychology, MedicineScience
- 16 April 2016
It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology
- J. Chapuis, F. Hansmannel, J. Lambert
- BiologyMolecular Psychiatry
- 12 February 2013
BIN1 transcript levels were increased in AD brains and a novel 3 bp insertion allele upstream of BIN1 was identified, which increased transcriptional activity in vitro and expression levels in human brain and AD risk in three independent case-control cohorts.
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
- R. Sims, S. J. van der Lee, G. Schellenberg
- BiologyNature Genetics
- 17 July 2017
Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
New insights into the genetic etiology of Alzheimer’s disease and related dementias
- C. Bellenguez, Fahri Küçükali, J. Lambert
- BiologyNature Genetics
- 1 April 2022
Meta-analysis of genome-wide association studies on Alzheimer's disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.
A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease
- Kuan-lin Huang, E. Marcora, A. Goate
- BiologyNature Neuroscience
- 19 June 2017
Results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function, and experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells.
Implication of the immune system in Alzheimer's disease: evidence from genome-wide pathway analysis.
- J. Lambert, B. Grenier‐Boley, P. Amouyel
- BiologyJournal of Alzheimer's Disease
- 13 June 2010
A systematic search for biological pathways using GWAS data set seems to comfort the primary causes already suspected but may specifically highlight the importance of the immune system in AD.
Tau deletion promotes brain insulin resistance
- Elodie Marciniak, A. Leboucher, D. Blum
- Biology, PsychologyJournal of Experimental Medicine
- 7 August 2017
A novel function of tau in its ability to regulate brain insulin signaling is uncovered and the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer’s disease patients is raised.
Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation
The Alzheimer’s Disease Sequencing Project undertook whole exome sequencing in 5,740 late-onset Alzheimer disease cases and 5,096 cognitively normal controls primarily of European ancestry, identifying novel and predicted functional genetic variants in genes previously associated with AD.
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