The Differential Influence of Immune, Endocytotic, and Lipid Metabolism Genes on Amyloid Deposition and Neurodegeneration in Subjects at Risk of Alzheimer's Disease.
J Alzheimers Dis
; 79(1): 127-139, 2021.
Article
em En
| MEDLINE
| ID: mdl-33216025
ABSTRACT
BACKGROUND:
Over 20 single-nucleotide polymorphisms (SNPs) are associated with increased risk of Alzheimer's disease (AD). We categorized these loci into immunity, lipid metabolism, and endocytosis pathways, and associated the polygenic risk scores (PRS) calculated, with AD biomarkers in mild cognitive impairment (MCI) subjects.OBJECTIVE:
The aim of this study was to identify associations between pathway-specific PRS and AD biomarkers in patients with MCI and healthy controls.METHODS:
AD biomarkers ([18F]Florbetapir-PET SUVR, FDG-PET SUVR, hippocampal volume, CSF tau and amyloid-ß levels) and neurocognitive tests scores were obtained in 258 healthy controls and 451âMCI subjects from the ADNI dataset at baseline and at 24-month follow up. Pathway-related (immunity, lipid metabolism, and endocytosis) and total polygenic risk scores were calculated from 20 SNPs. Multiple linear regression analysis was used to test predictive value of the polygenic risk scores over longitudinal biomarker and cognitive changes.RESULTS:
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. Total, immune, and lipid scores were associated with significant changes in cognitive measures, amyloid deposition, and brain metabolism.CONCLUSION:
Polygenic risk scores highlights the influence of specific genes on amyloid-dependent and independent pathways; and these pathways could be differentially influenced by lipid and immune scores respectively.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Peptídeos beta-Amiloides
/
Endocitose
/
Metabolismo dos Lipídeos
/
Doença de Alzheimer
/
Disfunção Cognitiva
/
Imunidade
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido