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 ;
Close
Infectious Diseases, Department of, Finsencentret, Rigshospitalet, The Capital Region of Denmark
Aznar, S ;
Close
Neurology, Department of, The Neuroscience Center, Rigshospitalet, The Capital Region of Denmark
Knudsen, G M ;
Close
0000-0003-1508-6866
Neurology, Department of, The Neuroscience Center, Rigshospitalet, The Capital Region of Denmark
Klein, A B
Close
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:

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

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

Full text access

On-site access

At institution

Metrics

Example	Finds records
water{}	containing the word "water".
water supplies"{}"	containing the phrase "water supplies".
author:"Doe, John"author:"{}"	containing the phrase "Doe, John" in the author field.
title:IEEEtitle:{}	containing the word "IEEE" in the title field.
bech{}	containing the word "bech".
marie bech"{}"	containing the phrase "marie bech".
orcid:0000-0002-5429-5292orcid:{}	Having a particular ORCID
Need more help?	Advanced search tutorial