Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.371286v1?rss=1 Authors: Paliwal, D., McInerney, T. W., Pa, J., Swerdlow, R. H., Easteal, S., Andrews, S. J. Abstract: INTRODUCTION: Genetic, animal and epidemiological studies involving biomolecular and clinical endophenotypes implicate mitochondrial dysfunction in Alzheimers 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. METHODS: We investigated associations of PRS for genes involved in 12 mitochondrial pathways (pathway-PRS) related to AD in 854 participants from Alzheimers Disease Neuroimaging Initiative. RESULTS: Pathway-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]). DISCUSSION: Therapeutic 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. Copy rights belong to original authors. Visit the link for more info