Although no individual voxel passed multiple-testing correction, we found significant spatial overlap between the effects of AD risk loci on VBM and the expression of genes (MEF2C, CLU, and SLC24A4) in the Allen Brain Atlas.
Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup.
Single nucleotide polymorphisms (SNPs) in and near ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, complement receptor 1 (CR1), EPHA1, EXOC3L2, FERMT2, HLA cluster (DRB5-DQA), INPP5D, MEF2C, MS4A cluster (MS4A3-MS4A6E), NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1 have been associated with Alzheimer's disease (AD) in large meta-analyses.
Multivariate analysis might suggest that regular "mind-body" religious meditative activities may be negatively associated with AD in this population, as well as the CLU genotype at rs9331888.
Although the actual risk-increasing polymorphisms at this locus remain to be identified, we previously observed an increased frequency of rare non-synonymous mutations and small insertion-deletions of CLU in AD patients, which specifically clustered in the β-chain domain of CLU.
In the present study, we try to review the inflammation in AD and immunity-associated GWAS risk genes like HLA-DRB5/DRB1, INPP5D, MEF2C, CR1, CLU and TREM2.
Refinements of clinical tests used as outcome measures such as clinical dementia rating-sum of boxes further reduced sample sizes; (7) the pioneering of genome-wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci, CR1, CLU, and PICALM and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI-like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker and clinical data to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (10) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world.
In this case-control study, we aimed to investigate whether single nucleotide polymorphisms in MTHFR (rs1801133), PICALM (3851719), CLU (rs11136000), and CR1 (rs6701713) are associated with AD.
Remarkably, the expression of a number of genes known to be involved in AD, such as APP, PSEN1, PSEN2, TTR and CLU is moderate to high and remains stable in both healthy and affected CPE.
These loci are in or near-novel AD genes including BIN1, CR1, CLU, phosphatidylinositol-binding clathrin assembly protein (PICALM), CD33, EPHA1, MS4A4/MS4A6, ABCA7, CD2AP, SORL1, HLA-DRB5/DRB1, PTK2B, SLC24A4-RIN3, INPP5D, MEF2C, NME8, ZCWPW1, CELF1, FERMT2, CASS4, and TRIP4 and each has small effects on risk of AD (relative risks of 1.1-1.3).
In conclusion, accumulation of Aβ, in combination with clusterin, within and around cerebral capillaries, may further aggravate the disease process in AD by affecting P-gp expression.
We tracked the volume of the lateral ventricles across baseline, 1-year, and 2-year follow-up scans in a large sample of elderly human participants (N = 736 at baseline), from the Alzheimer's Disease Neuroimaging Initiative, to determine whether these CLU risk variants predicted longitudinal ventricular expansion.
Collectively, our findings from this meta-analysis indicate that the effect of the CLUrs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.