Dataset Information

Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.

ABSTRACT: APOE is the only gene that has been consistently replicated as a risk factor for late onset Alzheimer's disease. Several recent studies have identified linkage to chromosome 10 for both risk and age of onset, suggesting that this region harbours genes that influence the development of the disease. A recent study reported association between single nucleotide polymorphisms (SNPs) in the VR22 gene (CTNNA3) on chromosome 10 and plasma levels of Abeta42, an endophenotype related to Alzheimer's disease.To assess whether polymorphisms in the VR22 gene are associated with Alzheimer's disease in a large sample of Alzheimer's disease families and an independent set of unrelated cases and controls.Several SNPs showed association in either the family based or case-control analyses (p<0.05). The most consistent findings were with SNP6, for which there was significant evidence of association in both the families and the unrelated cases and controls. Furthermore, there was evidence of significant interaction between APOE-4 and two of the VR22 SNPs, with the strongest evidence of association being concentrated in individuals carrying APOE-4.This study suggests that VR22 or a nearby gene influences susceptibility to Alzheimer's disease, and the effect is dependent on APOE status.

SUBMITTER: Martin ER

PROVIDER: S-EPMC1735932 | biostudies-other | 2005 Oct

REPOSITORIES: biostudies-other

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Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.

Martin E R ER Bronson P G PG Li Y-J YJ Wall N N Chung R-H RH Schmechel D E DE Small G G Xu P-T PT Bartlett J J Schnetz-Boutaud N N Haines J L JL Gilbert J R JR Pericak-Vance M A MA

Journal of medical genetics 20051001 10

<h4>Background</h4>APOE is the only gene that has been consistently replicated as a risk factor for late onset Alzheimer's disease. Several recent studies have identified linkage to chromosome 10 for both risk and age of onset, suggesting that this region harbours genes that influence the development of the disease. A recent study reported association between single nucleotide polymorphisms (SNPs) in the VR22 gene (CTNNA3) on chromosome 10 and plasma levels of Abeta42, an endophenotype related t ...[more]

PMID: 16199552

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Project description:BACKGROUND:Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ?4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear. OBJECTIVE:We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ?4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ?4, Lewy bodies, and psychosis. METHODS:Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ?4, as well as their interaction. RESULTS:Psychosis and the presence of APOE ?4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ?4 on MMSE scores, with APOE ?4 negatively affecting patients with hallucinations-only psychosis. APOE ?4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. CONCLUSION:Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ?4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ?4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.

Dataset Information

Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.

Publications

Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.

Similar Datasets

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