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

Autor: Sepulveda-Falla D; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia., Vélez JI; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia.; Universidad del Norte, Barranquilla, Colombia., Acosta-Baena N; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia., Baena A; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia., Moreno S; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia., Krasemann S; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lopera F; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia., Mastronardi CA; Genomics and Predictive Medicine Group, Department of Genome Sciences, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.; INPAC Research Group, Fundación Universitaria Sanitas, Bogotá, Colombia., Arcos-Burgos M; Grupo de Investigación en Psiquiatría (GIPSI), Departamento de Psiquiatría, Facultad de Medicina, Instituto de Investigaciones Médicas, Universidad de Antioquia, Medellín, Colombia.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Apr; Vol. 20 (4), pp. 2873-2885. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1002/alz.13754
Abstrakt: Introduction: Rate 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.
Methods: RCD 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.
Results: One 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.
Discussion: Impaired 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.
(© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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