The major Alzheimer's disease susceptibility genes (APOE, clusterin, complement receptor 1 (CR1) and phosphatidylinositol binding clathrin assembly protein, PICALM) can be implicated directly (APOE, CR1) or indirectly (clusterin and PICALM) in the herpes simplex life cycle.
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.
A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians.
Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.
To determine whether genetic variants in CLU, CR1, and PICALM confer risk for AD in independent data sets (n = 4254) and to test the impact of these markers on cerebrospinal fluid (CSF)-Aβ42 and total-tau protein levels (n = 425).
How precisely the different functional role of CR1-S in the immune complement cascade contributes to AD pathogenesis will need additional functional studies.
Our main findings were i) we were able to build generalizable models with clinically relevant accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting progression; iii) our methodology allowed us to discover that expression of CR1 (complement receptor 1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive value.
We investigated the influence of the rs6656401 single nucleotide polymorphisms (SNP) of the CR1 gene, the rs3851179 SNP of the PICALM gene, and the rs11136000 SNP of the CLU gene on risk of AD in a Polish population.
These observations indicate that AD susceptibility is associated with the long CR1 isoform (CR1*2), albeit at a lower density, suggesting that AD results from insufficient clearance of plaque deposits rather than increased inflammation.
Genetic polymorphisms in several genes, including APOE (Apolipoprotein E), PSEN1 (Presenilin 1), CR1 (Complement receptor 1), and PICALM (Phosphatidylinositol binding clathrin assembly protein), have been associated to an increased AD risk.
The AD susceptibility genes apolipoprotein E (<i>APOE</i>), phosphatidylinositol binding clathrin assembly protein (<i>PICALM</i>), complement receptor 1 (<i>CR1</i>) and clusterin (<i>CLU</i>) are involved in the HSV lifecycle.
Accumulated evidence suggests that a variant within the CR1 gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences β-amyloid (Aβ) deposition in brain tissue.