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Neurites containing the neurofilament-triplet proteins are selectively vulnerable to cytoskeletal pathology in Alzheimer's disease and transgenic mouse models

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posted on 2023-05-17, 20:15 authored by Mitew, S, Matthew KirkcaldieMatthew Kirkcaldie, Tracey DicksonTracey Dickson, James VickersJames Vickers
Amyloid-β plaque accumulation in Alzheimer's disease (AD) is associated with dystrophic neurite (DN) formation and synapse loss in principal neurons, but interneuron pathology is less clearly characterized. We compared the responses of neuronal processes immunoreactive for either neurofilament triplet (NF+) or calretinin (CR+) to fibrillar amyloid (Aβ) plaques in human end-stage and preclinical AD, as well as in APP/PS1 and Tg2576 transgenic mouse AD models. Neurites traversing the Aβ plaque core, edge, or periphery, defined as 50, 100, and 150% of the plaque diameter, respectively, in human AD and transgenic mouse tissue were compared to age-matched human and wild-type mouse controls. The proportion of NF+ neurites exhibiting dystrophic morphology (DN) was significantly larger than the proportion of dystrophic CR+ neurites in both human AD and transgenic mice (p < 0.01). Additionally, the number of NF+, but not CR+, DNs, correlated with Aβ plaque size. We conclude that CR+ interneurons appear to be more resistant than NF+ neurons to AD-mediated cytoskeletal pathology.

History

Publication title

Frontiers in Neuroanatomy

Volume

7

Article number

30

Number

30

Pagination

1-10

ISSN

1662-5129

Department/School

Tasmanian School of Medicine

Publisher

Frontiers Research Foundation

Place of publication

Switzerland

Rights statement

Copyright © 2013 Mitew, Kirkcaldie, Dickson and Vickers. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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