Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer's disease?

Götz, Jürgen, Ittner, Lars M. and Kins, Stefan (2006) Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer's disease?. Journal of Neurochemistry, 98 4: 993-1006. doi:10.1111/j.1471-4159.2006.03955.x


Author Götz, Jürgen
Ittner, Lars M.
Kins, Stefan
Title Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer's disease?
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 1471-4159
0022-3042
ISBN 978-981-4316-01-9
Publication date 2006-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1111/j.1471-4159.2006.03955.x
Open Access Status Not Open Access
Volume 98
Issue 4
Start page 993
End page 1006
Total pages 14
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
The subcellular localization of organelles, mRNAs and proteins is particularly challenging in neurons. Owing to their extended morphology, with axons in humans exceeding a meter in length, in addition to which they are not renewed but persist for the entire lifespan, it is no surprise that neurons are highly vulnerable to any perturbation of their sophisticated transport machinery. There is emerging evidence that impaired transport is not only causative for a range of motor disorders, but possibly also for Alzheimer's disease (AD) and related neurodegenerative disorders. Support for this hypothesis comes from transgenic animal models. Overexpression of human tau and amyloid precursor protein (APP) in mice and flies models the key hallmark histopathological characteristics of AD, such as somatodendritic accumulation of phosphorylated forms of tau and β-amyloid (Aβ) peptide-containing amyloid plaques, as well as axonopathy. The latter has also been demonstrated in mutant mice with altered levels of Alzheimer-associated genes, such as presenilin (PS). In Aβ-producing APP transgenic mice, axonopathy was observed before the onset of plaque formation and tau hyperphosphorylation. In human AD brain, an axonopathy was revealed for early but not late Braak stages. The overall picture is that key players in AD, such as tau, APP and PS, perturb axonal transport early on in AD, causing impaired synaptic plasticity and reducing survival rates. It will be challenging to determine the molecular mechanisms of these different axonopathies, as this might assist in the development of new therapeutic strategies.
Keyword Biochemistry & Molecular Biology
Clinical Neurology
Biochemistry & Molecular Biology
Neurosciences & Neurology
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Thu, 27 Feb 2014, 20:33:49 EST by Ms Kate Rowe on behalf of Queensland Brain Institute