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• W2897572742 abstract "With the increasing number of failed treatments in Alzheimer's disease (AD), research has progressed towards the identification of preclinical subjects with increased risk for dementia. Genetic information, such as the presence of the E4 allele of apolipoprotein E (APOE), can help identify subjects at higher risk for AD. In the last decade, genome-wide association studies have identified over 20 single nucleotide polymorphisms associated with increased risk of dementia. These risk loci can ultimately be categorised into three main pathways: immunity, lipid metabolism and endocytosis that influence AD pathology. This study aims to compare polygenic risk scores calculated from 20 identified risk loci, with pathological substrates of AD in a population of mild cognitive impairment (MCI) subjects. Data from 258 healthy controls (HC) and 451 MCI subjects were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI) database, with a 24months follow up. Polygenic immune, endocytotic, lipid and total risk score were calculated and 10th and 90th percentiles values of each score were compared. Data from AV45-PET, FDG-PET, MRI scans, CSF tau and amyloid beta, neurocognitive tests (ADAS COG-13, CDR-SB, MMSE) and hippocampal volume were obtained. Subjects with higher (90th percentile) total risk score had significantly increased amyloid deposition (10%, p<.05), higher CSF tau levels (128%, p<.05) and worse cognitive profile (22% ADAS13 score increase, p<.05) compared to those with lower (10th percentile) total risk score. Higher immune risk score was associated with worse cognitive measures and reduced glucose metabolism. Higher lipid risk score was associated with increased amyloid deposition and cortical hypometabolism, while no significant associations were demonstrated for the endocytotic score. Longitudinally, the total, immune and lipid scores were associated with significant changes in cognitive measures, amyloid deposition and brain metabolism. This study highlights the fact that polygenic risk scores are a good indicator of AD risk. This is the first study that highlights that immune pathway may influence neurodegeneration affecting amyloid independent pathway, while lipid pathway may be influencing AD through amyloid dependent pathway. This may open doors to potential therapeutics targeting immunity, endocytosis and lipid metabolism." @default.
• W2897572742 created "2018-10-26" @default.
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• W2897572742 date "2018-07-01" @default.
• W2897572742 modified "2023-10-16" @default.
• W2897572742 title "O2‐15‐01: THE DIFFERENTIAL INFLUENCE OF IMMUNE, ENDOCYTOTIC AND LIPID METABOLISM GENES ON AMYLOID DEPOSITION AND NEURODEGENERATION IN ALZHEIMER'S DISEASE" @default.
• W2897572742 doi "https://doi.org/10.1016/j.jalz.2018.06.2724" @default.
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