Genetic modifiers of cognitive decline in <i>PSEN1</i> E280A Alzheimer's disease-Reference-Cited by-同舟云学术

Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease

Published:2024-03-07 Issue:4 Volume:20 Page:2873-2885
ISSN:1552-5260
Container-title:Alzheimer's & Dementia
language:en
Short-container-title:Alzheimer's & Dementia

Author:

Sepulveda‐Falla Diego¹²^ORCID,Vélez Jorge I.²³,Acosta‐Baena Natalia²,Baena Ana²,Moreno Sonia²,Krasemann Susanne¹,Lopera Francisco²,Mastronardi Claudio A.⁴⁵,Arcos‐Burgos Mauricio⁶

Affiliation:

1. Institute of Neuropathology University Medical Center Hamburg‐Eppendorf Hamburg Germany

2. Grupo de Neurociencias de Antioquia Universidad de Antioquia Medellín Colombia

3. Universidad del Norte Barranquilla Colombia

4. Genomics and Predictive Medicine Group Department of Genome Sciences John Curtin School of Medical Research The Australian National University Canberra Australia

5. INPAC Research Group, Fundación Universitaria Sanitas Bogotá Colombia

6. Grupo de Investigación en Psiquiatría (GIPSI) Departamento de Psiquiatría Facultad de Medicina Instituto de Investigaciones Médicas Universidad de Antioquia Medellín Colombia

Abstract

AbstractINTRODUCTIONRate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD.METHODSRCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole‐exome sequencing for association with common exonic functional variants. Findings were validated in post mortem brain tissue.RESULTSOne hundred seventy‐two gene variants in FAD, and 227 gene variants in SAD associated with RCD. In FAD, performance decline of the immediate recall of the Rey‐Osterrieth figure test associated with 122 genetic variants. Olfactory receptor OR51B6 showed the highest number of associated variants. Its expression was detected in temporal cortex neurons.DISCUSSIONImpaired olfactory function has been associated with cognitive impairment in AD. Genetic variants in these or other genes could help to identify risk of faster memory decline in FAD and SAD patients.

Funder

Australian National University

Universidad de Antioquia

Publisher

Wiley

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