PICALM and CR1 Variants are not Associated with Sporadic Alzheimer's Disease in Chinese Patients.

As with pre GWAS studies, the problems of replication will not go away. It is quite possible that there are many ways of causing Alzheimer's disease, particularly because of the organisation of gene subsets into signalling networks, and because of relationships betwen genes and risk factors.

Risk factors: Alzheimer's : Kegg pathways Alzheimer's

Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

This study confirmed APOE , clusterin , complement receptor 1 and PICALM, and also angiotensin converting enzyme ACE and cystatin CST3 as Alzheimer's disease risk factors

However, note that PICALM did not turn up positive in a chinese study Yu et al, 20101  supporting the notion that genetic associations may cluster in geographical hot and cold spots.  See database

PICALM is not associated with Alzheimer's disease in China

PICALM

Distribution and Expression of Picalm in Alzheimer Disease.

Distribution and Expression of Picalm in Alzheimer... [J Neuropathol Exp Neurol. 2010] - PubMed result

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APP, APOE, Complement receptor 1, Clusterin and PICALM and their involvement in the Herpes simplex life-cycle

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. The virus binds to proteoliposomes containing APOE or APOA1 and also to CR1, and both clusterin and PICALM are related to a mannose 6-phosphate receptor used by the virus for cellular entry and intracellular transport. PICALM also binds to a nuclear exportin used by the virus for nuclear egress. Clusterin and complement receptor 1 are both related to the complement pathways and play a general role in pathogen defence. In addition, the amyloid precursor protein APP is involved in Herpes viral transport and gamma-secretase cleaves a number of receptors used by the virus for cellular entry. APOE , APOA1 and clusterin, or alpha 2-macroglobulin, insulysin and caspase 3, which also bind to the virus, are involved in beta-amyloid clearance or degradation, as are the viral binding complement components, C3 and CR1. There are multiple ways in which the products of key susceptibility genes might be able to modify the viral life cycle and in turn the virus interacts with key proteins involved in APP and beta-amyloid processing. These interactions support a role for the Herpes simplex virus in Alzheimer’s disease pathology and suggest that antiviral agents or vaccination might be considered as viable therapeutic strategies in Alzheimer’s disease.
Neuroscience Letters 2010

APOE, Clusterin, PICALM, complement receptor 1 and other genes involved in the Herpes simplex life cycle

apoe complement receptor 1  clusterin    PICALM