Oligodendrocytes damage in Alzheimer's disease: beta amyloid toxicity and inflammation.
Research on Alzheimer's disease (AD) focuses mainly on neuronal death and synaptic impairment induced by beta-Amyloid peptide (Abeta), events at least partially mediated by astrocyte and microglia activation. However, substantial white matter damage and its consequences on brain function warrant the study of oligodendrocytes participation in the pathogenesis and progression of AD. Here, we analyze reports on oligodendrocytes' compromise in AD and discuss some experimental data indicative of Abeta toxicity in culture. We observed that 1 microM of fibrilogenic Abeta peptide damages oligodendrocytes in vitro: while pro-inflammatory molecules (1 microg/ ml LPS + 1 ng/ml IFNgamma) or the presence of astrocytes reduced the Abeta-induced damage. This agrees with our previous results showing an astrocyte-mediated protective effect over Abeta-induced damage on hippocampal cells and modulation of the activation of microglial cells in culture. Oligodendrocytes protection by astrocytes could be, either by reduction of Abeta fibrilogenesis/deposition or prevention of oxidative damage. Likewise, the decrease of Abeta-induced damage by proinflammatory molecules could reflect the production of trophic factors by activated oligodendrocytes and/or a metabolic activation as observed during myelination. Considering the association of inflammation with neurodegenerative diseases. oligodendrocytes impairment in AD patients could potentiate cell damage under pathological conditions.
Roth
Alejandro D
AD
Laboratory Neuroscience, Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Ramírez
Gigliola
G
Alarcón
Rodrigo
R
Von Bernhardi
Rommy
R
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D016923:Cell Death; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D051381:Rats
D016229:Amyloid beta-Peptides