The phosphatidylinositol binding clathrin assembly protein (PICALM) is involved in clathrin-mediated endocytosis and polymorphisms in and near the gene locus were identified as genetic risk factors for AD.
<b>Background:</b> Phosphatidylinositol binding clathrin assembly protein (<i>PICALM</i>) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk.
Late-onset AD risk factor Phosphatidylinositol binding clathrin assembly protein (PICALM) is associated with both ABCB1/P-gp and LRP1 representing a functional link and guiding both proteins through the brain endothelium.
Here we focus on CALM, a protein containing an ANTH domain, which is implicated in the pathogenesis of blood cancers and Alzheimer disease, and discuss how alteration of CALM function is involved in these diseases.
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.
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.
Phosphatidylinositol-binding clathrin assembly protein (PICALM) (rs3851179) has been associated with AD; in particular, the A allele may serve a protective role, while the G allele serves as a strong genetic risk factor.
The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism-gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT).
The increase in beta relative power in the carriers of the AD risk PICALM GG genotype suggests changes in the cortical excitatory-inhibitory balance, which are heightened during normal aging.
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.
Moreover, reduction of CALM decreases Aβ deposition as well as brain levels of insoluble Aβ42 in vivo These results suggest that CALM expression modifies AD risk by regulating Aβ pathology.
We have investigated the involvement of PICALM in the processing of amyloid precursor protein (APP) to understand how PICALM could be linked to the development of AD.
Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.
In summary, this updated meta-analysis highlights the involvement of PICALMrs3851179 variant in Alzheimer's disease susceptibility in Chinese population.
To examine whether there is a genetic link for these diseases, we performed a case-control study in Chinese population to evaluate the association of AD genome-wide association studies top hits with both PD and cognitive function in PD, investigating 13 single-nucleotide polymorphisms in 9 genes (BIN1, CLU, ABCA7, CR1, PICALM, MS4A6A, CD33, MS4A4E, and CD2AP).
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.