Neurofilament light gene deletion exacerbates amyloid, dystrophic neurite, and synaptic pathology in the APP/PS1 transgenic model of Alzheimer's disease

Neurobiology of Aging
Carmen M Fernandez-MartosJ C Vickers

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with the loss of cognitive function. Neurofilament (NF) triplet proteins, the major structural (intermediate filament) proteins of neurons, are expressed in a subset of pyramidal cells that show a high degree of vulnerability to degeneration in AD. Alterations in the NF triplet proteins in amyloid-beta (Aβ) plaque-associated dystrophic neurites (DNs) represent the first cytoskeletal aberration to occur in the neocortex in the earliest stages of AD. We generated transgenic APP/PS1 (APPswe/PSEN1dE9) mice on the neurofilament light knockout (NFL KO) background to explore the role of NFL deletion in the context of DN formation, synaptic changes, and other neuropathologic features. Our analysis demonstrated that NFL deficiency significantly increased neocortical DN pathology, Aβ deposition, synapse vulnerability, and microgliosis in APP/PS1 mice. Thus, NFs may have a role in protecting neurites from dystrophy and in regulating cellular pathways related to the generation of Aβ plaques.

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Citations

Oct 26, 2016·Brain Research Bulletin·Aidong Yuan, Ralph A Nixon
Mar 17, 2018·Metabolic Brain Disease·Anna KingCarmen Fernandez-Martos
Oct 27, 2017·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Carmen M Fernandez-MartosJames C Vickers
Feb 17, 2019·Cellular and Molecular Life Sciences : CMLS·Kunal DhimanVeer Bala Gupta
Jan 8, 2021·Disease Models & Mechanisms·Rachel AtkinsonAnna King

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