Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid
β-peptide (Aβ) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of
neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to Aβ are still elusive.
Here, we tested the role of Aβ in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes
and in organotypic cerebellar slices. We found that Aβ peptides specifically induced local translation of 18.5-kDa
myelin basic protein (MBP) isoform in distal cell processes concomitant with an increase of process complexity of MBPexpressing
oligodendrocytes. Aβ oligomers required integrin β1 receptor, Src-family kinase Fyn and Ca2+/CaMKII as
effectors to modulate MBP protein expression. The pharmacological inhibition of Fyn kinase also attenuated
oligodendrocyte differentiation and survival induced by Aβ oligomers. Similarly, using ex vivo organotypic cerebellar
slices Aβ promoted MBP upregulation through Fyn kinase, and modulated oligodendrocyte population dynamics by
inducing cell proliferation and differentiation. Importantly, application of Aβ to cerebellar organotypic slices enhanced
remyelination and oligodendrocyte lineage recovery in lysolecithin (LPC)-induced demyelination. These data reveal an
important role of Aβ in oligodendrocyte lineage function and maturation, which may be relevant to AD pathogenesis.
