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BMC Neuroscience

, 8:29

First Online: 02 May 2007Received: 06 December 2006Accepted: 02 May 2007

Abstract

BackgroundAggregation of the amyloid peptides, Aβ40 and Aβ42, is known to be involved in the pathology of Alzheimer-s disease AD. Here we investigate the relationship between peptide aggregation and cell surface binding of three forms of Aβ Aβ40, Aβ42, and an Aβ mutant.

ResultsUsing confocal microscopy and flow cytometry with fluorescently labelled Aβ, we demonstrate a correlation between the aggregation propensity of the Alzheimer amyloid peptides and their neuronal cell surface association. We find that the highly aggregation prone Aβ42 associates with the surface of neuronal cells within one hour, while the less aggregation prone Aβ40 associates over 24 hours. We show that a double mutation in Aβ42 that reduces its aggregation propensity also reduces its association with the cell surface. Furthermore, we find that a cell line that is resistant to Aβ cytotoxicity, the non-neuronal human lymphoma cell line U937, does not bind either Aβ40 or Aβ42.

ConclusionTaken together, our findings reveal that amyloid peptide aggregation propensity is an essential determinant of neuronal cell surface association. We anticipate that our approach, involving Aβ imaging in live cells, will be highly useful for evaluating the efficacy of therapeutic drugs that prevent toxic Aβ association with neuronal cells.

Abbreviations7-AAD7-Aminoactinomycin D

ADAlzheimer-s disease

Aβamyloid β

APPamyloid precursor protein

CDcircular dichroism

DMEM-F12Dulbecco-s modified eagle-s medium: nutrient mixture F-12 1:1 mixture

D-PBSDulbecco-s phosphate-buffered saline

EDTAethylenediaminetetraacetic acid

FITCfluorescein isothiocyanate

GFPgreen fluorescent protein

MALDImatrix assisted laser desorption-ionization

NGFnerve growth factor

N2Aneuroblastoma-2A

PC12rat adrenal pheochromocytoma

SBTIsoybean trypsin inhibitor

TMRtetramethylrhodamine.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-8-29 contains supplementary material, which is available to authorized users.

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Autor: David A Bateman - JoAnne McLaurin - Avijit Chakrabartty

Fuente: https://link.springer.com/







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