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

Citation

Fernandez-Martos, CM and King, AE and Atkinson, RAK and Woodhouse, A and Vickers, JC, Neurofilament light gene deletion exacerbates amyloid, dystrophic neurite, and synaptic pathology in the APP/PS1 transgenic model of Alzheimer's disease, Neurobiology of Aging, 36, (10) pp. 2757-2767. ISSN 0197-4580 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Elsevier Inc.

DOI: doi:10.1016/j.neurobiolaging.2015.07.003

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.

Item Details

Item Type:Refereed Article
Keywords:Alzheimer's disease, neurofilaments, plaques, synapses
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Fernandez-Martos, CM (Dr Carmen Fernandez-Martos)
Author:King, AE (Associate Professor Anna King)
Author:Atkinson, RAK (Ms Rachel Atkinson)
Author:Woodhouse, A (Dr Adele Woodhouse)
Author:Vickers, JC (Professor James Vickers)
ID Code:104622
Year Published:2015
Web of Science® Times Cited:11
Deposited By:Medicine (Discipline)
Deposited On:2015-11-17
Last Modified:2018-03-20
Downloads:0

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