Signatures for viral infection and inflammation in the proximal olfactory system in familial Alzheimer's disease.

Autor: Bubak AN; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Merle L; Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Niemeyer CS; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Baxter BD; Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Gentile Polese A; Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Ramakrishnan V; Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Gomez J; Neuroscience Research Group, University of Antioquia, Medellín, Colombia., Madrigal L; Neuroscience Research Group, University of Antioquia, Medellín, Colombia., Villegas-Lanau A; Neuroscience Research Group, University of Antioquia, Medellín, Colombia., Lopera F; Neuroscience Research Group, University of Antioquia, Medellín, Colombia., Macklin W; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Frietze S; Department of Medical Laboratory Sciences, University of Vermont, Burlington, VT, USA., Nagel MA; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Opthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Restrepo D; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: diego.restrepo@cuanschutz.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2023 Mar; Vol. 123, pp. 75-82. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1016/j.neurobiolaging.2022.12.004
Abstrakt: Alzheimer's disease (AD) is characterized by deficits in olfaction and olfactory pathology preceding diagnosis of dementia. Here we analyzed differential gene and protein expression in the olfactory bulb (OB) and tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A mutation. Compared to control, FAD OT had increased immunostaining for β-amyloid (Aβ) and CD68 in high and low myelinated regions, as well as increased immunostaining for Iba1 in the high myelinated region. In FAD samples, RNA sequencing showed: (1) viral infection in the OB; (2) inflammation in the OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory; and (3) decreased oligodendrocyte deconvolved transcripts. Interestingly, spatial proteomic analysis confirmed altered myelination in the OT of FAD individuals, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation and dysregulation of myelination of the olfactory system may disrupt hippocampal function, contributing to acceleration of FAD progression.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: