Alzheimer's disease (AD) is a neurodegenerative disorder characterized by aggregation of β-amyloid peptide (Aβ) into senile plaques and cerebrovascular amyloid. It remains unclear if amyloid is initiated by the accumulation of Aβ in the extracellular space or by intraneuronal Aβ generation. In February 24 advanced online Nature Neuroscience, Melanie Meyer-Luehmann and colleagues at the University of Basel, Switzerland, show that diffusion of soluble Aβ in the extracellular space is involved in the spread of Aβ pathology, and that extracellular amyloid formation can lead to neurodegeneration (Nature Neuroscience, DOI:10.1038/nn1022, February 24, 2003).