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Dystrophic neurites in TgCRND8 and Tg2576 mice mimic human pathological brain aging

journal contribution
posted on 2023-05-17, 00:42 authored by Adele WoodhouseAdele Woodhouse, James VickersJames Vickers, Adlard, PA, Tracey DicksonTracey Dickson
The morphology and neurochemistry of β-amyloid (Aβ) plaque-associated dystrophic neurites present in TgCRND8 and Tg2576 mice was demonstrated to be strikingly similar to that observed in pathologically aged human cases, but not in Alzheimer’s disease (AD) cases. Specifically, pathologically aged cases and both transgenic mouse lines exhibited a-internexin- and neurofilament-triplet-labelled ring- and bulb-like dystrophic neurites, but no classical hyperphosphorylated-tau dystrophic neurite pathology. In contrast, AD cases demonstrated abundant classical hyperphosphorylated-tau-labelled dystrophic neurites, but no neurofilament-triplet-labelled ring-like dystrophic neurites. Importantly, quantitation demonstrated that the Aβ plaques in TgCRND8 mice were highly axonopathic, and localised displacement or clipping of apical dendrite segments was also associated with AB plaques in both transgenic mouse models. These results suggest that neuronal pathology in these mice represent an accurate and valuable model for understanding, and developing treatments for, the early brain changes of AD.

History

Publication title

Neurobiology of Aging

Volume

30

Issue

6

Pagination

864-874

ISSN

0197-4580

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Science Inc

Place of publication

360 Park Ave South, New York, USA, Ny, 10010-1710

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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