The microtubule-associated protein 1A (MAP1A) is an early molecular target of soluble Aβ-peptide

C Clemmensen; S Aznar; G M Knudsen; A B Klein

doi:10.1007/s10571-011-9796-9

The microtubule-associated protein 1A (MAP1A) is an early molecular target of soluble Aβ-peptide

Authors:

Clemmensen, C ;
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Infectious Diseases, Department of, Finsencentret, Rigshospitalet, The Capital Region of Denmark
Aznar, S ;
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Neurology, Department of, The Neuroscience Center, Rigshospitalet, The Capital Region of Denmark
Knudsen, G M ;
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0000-0003-1508-6866
Neurology, Department of, The Neuroscience Center, Rigshospitalet, The Capital Region of Denmark
Klein, A B
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0000-0002-0236-3089
Department of Clinical Physiology, Nuclear Medicine & PET, Centre of Diagnostic Investigations, Rigshospitalet, The Capital Region of Denmark

DOI:

10.1007/s10571-011-9796-9

Abstract:

A progressive accumulation of amyloid β-protein (Aβ) is widely recognized as a pathological hallmark of Alzheimer's disease (AD). Substantial progress has been made toward understanding the neurodegenerative cascade initiated by small soluble species of Aβ and recent evidence supports the notion that microtubule rearrangements may be proximate to neuritic degeneration and deficits in episodic declarative memory. Here, we examined primary cortical neurons for changes in markers associated with synaptic function following exposure to sublethal concentrations of non-aggregated Aβ-peptide. This data show that soluble Aβ species at a sublethal concentration induce degradation of the microtubule-associated protein 1A (MAP1A) without concurrently affecting dendritic marker MAP2 and/or the pre-synaptic marker synaptophysin. In addition, MAP1A was found to highly co-localize with the postsynaptic density-95 (PSD-95) protein, proposing that microtubule perturbations might be central for the Aβ-induced neuronal dysfunctions as PSD-95 plays a key role in synaptic plasticity. In conclusion, this study suggests that disruption of MAP1A could be a very early manifestation of Aβ-mediated synaptic dysfunction-one that presages the clinical onset of AD by years. Moreover, our data support the notion of microtubule-stabilizing agents as effective AD drugs.

Type:

Journal article

Language:

English

Published in:

Cellular and Molecular Neurobiology, 2012, Vol 32, Issue 4, p. 561-6

Keywords:

Alzheimer Disease; Amyloid beta-Peptides; Animals; Female; Memory, Episodic; Microtubule-Associated Proteins; Nerve Degeneration; Neurons; Pregnancy; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Solubility; Journal Article; Research Support, Non-U.S. Gov't

Main Research Area:

Medical science

Publication Status:

Published

Review type:

Peer Review

Submission year:

2012

Scientific Level:

Scientific

ID:

226420098

The microtubule-associated protein 1A (MAP1A) is an early molecular target of soluble Aβ-peptide

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