To explore mechanisms that may underlie associations between Alzheimer's disease (AD) and schizophrenia risk CLU gene and verbal memory, one of the most affected cognitive domains in both conditions, we studied DNA methylation in a region between AD-associated SNPs rs9331888 and rs9331896 in 72 healthy individuals and 73 schizophrenia patients.
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.
In peripheral blood, concentrations of CRP were elevated in AD (N<sub>AD</sub>/N<sub>HC</sub> = 3404/3332, SMD = 0.44, Z<sub>43</sub> = 3.43, p < 0.005; I<sup>2</sup> = 93.81%), but differences between groups in C3, C4, C1-inhibitor, SAP, factor H and clusterin concentrations were not significant, and inconsistent between studies.
Microglial activation as indicated by increased sTREM2 is present already at the preclinical SCD stage; increased MCP-1 and astroglial activation markers (YKL-40 and clusterin) were noted only at the MCI and AD dementia stages, respectively, and in Aβ+ cases (A+) with pathological T-tau (N+).
Subgroup analysis showed that the plasma CLU concentration was significantly increased only in the AD group (SDM = 1.85, 95% CI 0.84-2.85, P < 0.001), but not in MCI or other dementias.
In contrast, plasma Aβ42 showed a greater reduction over time in the prodromal AD than the "negative" aMCI group (p = 0.048), while CLU and Aβ40 increased, but similarly in the two groups.
These findings demonstrate that clusterin is necessarily involved in early stages of AD pathogenesis by enhancing toxic Aß pools to cause Aß-directed neurodegeneration and behavioral and cognitive impairments, but not in late stage.
In a multicenter case-control association study, we studied the SNPs rs11136000 (clusterin, CLU), rs541458 (phosphatidylinositol binding clatrin assembly protein, PICALM), and rs1554948 (transcription factor A, and tyrosine kinase, non-receptor, 1, TNK1) according to the three age groups 50-65 years (group 1), 66-80 years (group 2), and 80+ years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimer's disease (AD) patients.
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).
Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis.
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.
Since its discovery, numerous studies have linked clusterin expression deregulation with various physio-pathological processes such as cancer or Alzheimer's disease.
Since apoE and apoJ play an important role in the development of AD, we aimed to study the in vivo effect of the combined therapy of scFv-h3D6 with apoE and apoJ mimetic peptides (MPs).