scholarly journals Mitochondrial pathway‐specific Alzheimer’s disease polygenic risk scores are associated with increased risk of Alzheimer’s disease

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Devashi Paliwal ◽  
Shea J Andrews ◽  
Simon Easteal ◽  
Timothy McInerney
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Pathway ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Increased Risk

Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Hongliang Liu ◽  
Michael Lutz ◽  
Sheng Luo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Clinical Changes

Background: Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer’s disease (AD). Objective: In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. Methods: We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. Results: We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, se = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, se = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PIB and AV45), but decreased hippocampus and entorhinal cortex volumes (p <  0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ 42 (beta = 0.056, SE = 0.026, p = 0.036). Conclusion: Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.

The Differential Influence of Immune, Endocytotic, and Lipid Metabolism Genes on Amyloid Deposition and Neurodegeneration in Subjects at Risk of Alzheimer’s Disease

2021 ◽  
Vol 79 (1) ◽  
pp. 127-139
Author(s):  
Grazia Daniela Femminella ◽  
Denise Harold ◽  
James Scott ◽  
Julie Williams ◽  
Paul Edison ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Metabolism ◽  
Risk Score ◽  
Amyloid Deposition ◽  
Risk Scores ◽  
Healthy Controls ◽  
Cognitive Measures ◽  
Polygenic Risk ◽  
Increased Risk

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-β levels) and neurocognitive tests scores were obtained in 258 healthy controls and 451 MCI 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.

scholarly journals Mitochondrial pathway polygenic risk scores are associated with Alzheimer’s Disease

2020 ◽  
Author(s):  
Devashi Paliwal ◽  
Tim W. McInerney ◽  
Judy Pa ◽  
Russell H. Swerdlow ◽  
Simon Easteal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Membrane ◽  
Disease Risk ◽  
Epidemiological Studies ◽  
Mitochondrial Pathway ◽  
Risk Scores ◽  
Therapeutic Approaches ◽  
Polygenic Risk ◽  
Novel Approach

ABSTRACTINTRODUCTIONGenetic, animal and epidemiological studies involving biomolecular and clinical endophenotypes implicate mitochondrial dysfunction in Alzheimer’s disease (AD) pathogenesis. Polygenic risk scores (PRS) provide a novel approach to assess biological pathway-associated disease risk by combining the effects of variation at multiple, functionally related genes.METHODSWe investigated associations of PRS for genes involved in 12 mitochondrial pathways (pathway-PRS) related to AD in 854 participants from Alzheimer’s Disease Neuroimaging Initiative.RESULTSPathway-PRS for four mitochondrial pathways are significantly associated with increased AD risk: (i) response to oxidative stress (OR: 2.01 [95% Cl: 1.71, 2.37]); (ii) mitochondrial transport (OR: 1.81 [95% Cl: 1.55, 2.13]); (iii) hallmark oxidative phosphorylation (OR: 1.23 [95% Cl: 1.07, 1.41]); and (iv) mitochondrial membrane potential regulation (OR: 1.18 [95% Cl: 1.03, 1.36]).DISCUSSIONTherapeutic approaches targeting these pathways may have potential for modifying AD pathogenesis. Further investigation is required to establish a causal role for these pathways in AD pathology.

scholarly journals Pathway-Specific Polygenic Risk Scores as Predictors of Amyloid-β Deposition and Cognitive Function in a Sample at Increased Risk for Alzheimer’s Disease

2016 ◽  
Vol 55 (2) ◽  
pp. 473-484 ◽  
Author(s):  
Burcu F. Darst ◽  
Rebecca L. Koscik ◽  
Annie M. Racine ◽  
Jennifer M. Oh ◽  
Rachel A. Krause ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Amyloid Β ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Increased Risk

scholarly journals Mitochondrial pathway polygenic risk scores are associated with Alzheimer's Disease

2021 ◽  
Author(s):  
Devashi Paliwal ◽  
Tim W. McInerney ◽  
Judy Pa ◽  
Russell H. Swerdlow ◽  
Simon Easteal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Pathway ◽  
Risk Scores ◽  
Polygenic Risk

[P3-095]: THE USE OF POLYGENIC RISK SCORES (PRS) TO CHARACTERISE THE PRECLINICAL PHASE OF ALZHEIMER's DISEASE

2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P970-P971
Author(s):  
Michelle K. Lupton ◽  
Margie Wright ◽  
Nick Martin ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Preclinical Phase

scholarly journals Associations between Alzheimer’s disease polygenic risk scores and hippocampal subfield volumes in 17,161 UK Biobank participants

2021 ◽  
Vol 98 ◽  
pp. 108-115
Author(s):  
Heidi Foo ◽  
Anbupalam Thalamuthu ◽  
Jiyang Jiang ◽  
Forrest Koch ◽  
Karen A. Mather ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Scores ◽  
Uk Biobank ◽  
Polygenic Risk

P3-482: HIGHER ALZHEIMER'S DISEASE POLYGENIC RISK SCORES ARE ASSOCIATED WITH GREATER OBJECTIVELY MEASURED COGNITIVE EFFORT DESPITE NORMAL NEUROPSYCHOLOGICAL FUNCTION

2006 ◽  
Vol 14 (7S_Part_24) ◽  
pp. P1305-P1306
Author(s):  
William S. Kremen ◽  
Matthew S. Panizzon ◽  
Eric L. Granholm ◽  
Jeremy A. Elman ◽  
Daniel E. Gustavson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Effort ◽  
Risk Scores ◽  
Neuropsychological Function ◽  
Polygenic Risk ◽  
Objectively Measured

scholarly journals Defining Alzheimer’s disease subtypes using polygenic risk scores integrated with genomic and brain transcriptomic profiles

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Junming Hu ◽  
Jaeyoon Chung ◽  
Rebecca Panitch ◽  
Congcong Zhu ◽  
Gary W. Beecham ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Disease Subtypes
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