Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death.
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.
Although CLU has been considered as a therapeutic target in AD, cancer and dry eye, a role for clusterin in XFS/XFG needs to be better defined before therapeutic approaches involving CLU can be entertained.
Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3).
To examine whether a polygenic risk score (PRS) derived from <i>APOE4, CLU,</i> and <i>ABCA7</i> is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers.
Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease.
Plasma clusterin level showed an association with overall AD polygenic risk score, while clusterin, C1inh, and CRP levels each displayed some association with the inflammatory-specific AD polygenic risk score.
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.
The CLU gene could consistently affect the DMN FC with frontal regions among individuals at risk for Alzheimer's disease, and the CLU-T allele was associated with more compensatory neural processes in DMN changes.
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.
In this study, we aimed to investigate the functional significance of a clusterin intronic SNP, rs2279590, that has been associated with pseudoexfoliation, Alzheimer's disease (AD) and diabetes.
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.
There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).