Genetic risk prediction of late‐onset Alzheimer’s disease based on tissue‐specific transcriptomic analysis and polygenic risk scores

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Sang‐Hyuk Jung ◽  
Kwangsik Nho ◽  
Dokyoon Kim ◽  
Hong‐Hee Won ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Prediction ◽  
Genetic Risk ◽  
Late Onset ◽  
Transcriptomic Analysis ◽  
Risk Scores ◽  
Tissue Specific ◽  
Polygenic Risk ◽  
Genetic Risk Prediction

scholarly journals The use of genetic risk prediction to study prodromal Alzheimer’s disease in the PISA study

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Michelle K. Lupton ◽  
Amir Fazlollahi ◽  
Amelia Ceslis ◽  
Jurgen Fripp ◽  
Stephen Rose ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Prediction ◽  
Genetic Risk ◽  
Genetic Risk Prediction ◽  
Prodromal Alzheimer’S Disease

scholarly journals Polygenic Risk Score Effectively Predicts Risk of Depression Onset in Alzheimer’s Disease

2021 ◽  
Author(s):  
Suraj Upadhya ◽  
Hongliang Liu ◽  
Sheng Luo ◽  
Michael W. Lutz ◽  
Ornit Chiba-Falek
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Event Analysis ◽  
Polygenic Risk ◽  
Significant Performance

Abstract Introduction: Depression is a common, though heterogenous, comorbidity in late-onset Alzheimer’s Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiology between depression and LOAD. Collectively, this evidence suggested interactions between depression and LOAD. However, the underpinning genetic heterogeneity of depression co-occurrence with LOAD is largely unknown.Methods: Major Depressive Disorder (MDD) genome wide association study (GWAS) summary statistics were used to create polygenic risk scores (PRS). The Religious Orders Society and Rush Memory and Aging Project (ROSMAP) and National Alzheimer’s Coordinating Center (NACC) datasets were utilized to assess the PRS performance in predicting depression onset in LOAD patients.Results: The developed PRS showed marginal results in standalone models for predicting depression onset in both ROSMAP (AUC=0.540) and NACC (AUC=0.534). Full models, with baseline age, sex, education, and APOEε4 allele count, showed improved prediction of depression onset (ROSMAP AUC: 0.606, NACC AUC: 0.583). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P=0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in LOAD for both datasets (P<0.001 for all).Discussion: This study provided new insights into the genetic factors contributing to depression onset in LOAD and advanced our knowledge of the genetics underlying the heterogeneity of depression in LOAD. The developed PRS accurately predicted LOAD patients with depressive symptoms, thus, has clinical implications including, diagnosis of LOAD patients at high-risk to develop depression for early anti-depressant treatment.

P1-162: RISK PREDICTION OF ALZHEIMER'S DISEASE WITH AGE STRATIFICATION USING POLYGENIC RISK SCORES

2006 ◽  
Vol 14 (7S_Part_6) ◽  
pp. P339-P340 ◽  
Author(s):  
Jang Jae Lee ◽  
Sarang Kang ◽  
Wooje Lee ◽  
Tamil Iniyan Gunasekaran ◽  
Jungsoo Gim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Prediction ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Age Stratification

scholarly journals Interaction of Alzheimer’s Disease-Associated Genetic Risk with Indicators of Socioeconomic Position on Mild Cognitive Impairment in the Heinz Nixdorf Recall Study

2021 ◽  
pp. 1-11
Author(s):  
Mirjam Frank ◽  
Jonas Hensel ◽  
Lisa Baak ◽  
Sara Schramm ◽  
Nico Dragano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Socioeconomic Position ◽  
Genetic Risk ◽  
Late Onset ◽  
Heinz Nixdorf Recall Study ◽  
Low Education ◽  
Additive Scale

Background: The apolipoprotein E (APOE) ɛ4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI. Objective: To investigate whether APOE ɛ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort. Methods: Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOE ɛ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex. Results: Indication for interaction on the additive scale was found between APOE ɛ4 and low education on MCI (RERI: 0.52 [95% -confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOE ɛ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% -CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% -CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed. Conclusion: Results indicate that low education may have an impact on APOE ɛ4 expression on MCI, especially among women.

scholarly journals ApoE4 attenuates cortical neuronal activity and impairs memory in young apoE4 rats

2021 ◽  
Author(s):  
Ilona Har-Paz ◽  
Elor Arieli ◽  
Anan Moran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Neuronal Activity ◽  
Genetic Risk ◽  
Cortical Neurons ◽  
Late Onset ◽  
Genetic Risk Factor ◽  
Normal Brain ◽  
Brain Functions

AbstractThe E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD related neuropathology. Understanding these primary dysfunctions is vital for early detection of AD and the development of therapeutic strategies for it. Recently we have shown impaired extra-hippocampal memory in young apoE4 mice – a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we test the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 and wildtype rats, before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young apoE4 rats showed impaired CTA learning, consistent with our previous results in apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Single neuron and ensemble analyses of taste coding demonstrated that apoE4 neurons could be used to correctly classify tastes, but were unable to undergo plasticity to support learning. Our results suggest that apoE4 impacts brain excitability and plasticity early in life and may act as an initiator for later AD pathologies.Significant statementThe ApoE4 allele is the strongest genetic risk-factor for late-onset Alzheimer’s disease (AD), yet the link between apoE4 and AD is still unclear. Recent molecular and in-vitro studies suggest that apoE4 interferes with normal brain functions decades before the development of its related AD neuropathology. Here we recorded the activity of cortical neurons from young apoE4 rats during extra-hippocampal learning to study early apoE4 neuronal activity abnormalities, and their effects over coding capacities. We show that apoE4 drastically reduces basal and stimuli-evoked cortical activity in both excitatory and inhibitory neurons. The apoE4-induced activity attenuation did not prevent coding of stimuli identity and valence, but impaired capacity to undergo activity changes to support learning. Our findings support the hypothesis that apoE4 interfere with normal neuronal plasticity early in life; a deficit that may lead to late-onset AD development.

[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
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