Clusterin (apolipoprotein J), a multifunctional protein involved in amyloidogenesis in Alzheimer's disease, was studied immunohistochemically in both human transmissible spongiform encephalopathies (TSEs) and a mouse model of human TSE.
Clusterin is a glycosylated protein, and an alteration of its glycosylation in Alzheimer's disease might influence accurate quantification in cerebrospinal fluid through interference of antibody binding to the protein.
Clusterin (apolipoprotein J or ApoJ) is a complement inhibitor that appears to have a neuroprotective effect in response to tissue damage and has been reported to be upregulated in Alzheimer's disease.
Clusterin/apoJ is an intriguing gene frequently isolated by differential screening in laboratories from different areas of molecular biology, since it is overexpressed in numerous cases of degenerative diseases such as Alzheimer's disease and scrapie.
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 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.
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.
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 the exact contribution of these variants to altered AD risk is unclear, some have been linked to altered <i>CLU</i> expression at both mRNA and protein levels, altered cognitive and memory function, and altered brain structure.
Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ<sub>42</sub> (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau<sub>181</sub> levels (P = 0.009); larger studies are necessary to verify these results.
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).
By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE ε4 and a genetic risk score for AD (PICALM, BIN1, CLU) on episodic memory in general.