Accumulation of β-amyloid peptide (Aβ) in the brain is believed to trigger a complex and poorly understood pathologic reaction that results in the development of Alzheimer's disease (AD). Despite intensive study, there is no consensus as to how Aβ accumulation causes neurodegeneration in AD. In this issue of the JCI, Tesseur et al. report that the expression of TGF-β type II receptor (TβRII) by neurons is reduced very early in the course of AD and that reduced TGF-β signaling increased Aβ deposition and neurodegeneration in a mouse model of AD (see the related article beginning on page 3060). Intriguingly, reduced TGF-β signaling in neuroblastoma cells resulted in neuritic dystrophy and increased levels of secreted Aβ. Collectively, these data suggest that dysfunction of the TGF-β/TβRII signaling axis in the AD brain may accelerate Aβ deposition and neurodegeneration.
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