Abstract

Significance The amyloid-β (Aβ) peptide, which plays a central role in Alzheimer’s disease (AD) pathogenesis, exhibits many properties that are reminiscent of prions (self-propagating proteins that cause neurodegenerative disorders, such as mad cow disease). In the human prion diseases, distinct strains of prions can be distinguished, and therefore, we asked whether different strains of Aβ aggregates might exist in the brains of AD patients. Inoculation of transgenic mice with brain samples from patients with two different heritable forms of AD produced two distinct patterns of cerebral Aβ deposition, and these differences were maintained on serial passage. We conclude that distinct strains of Aβ can be discerned in AD patients, which may help to explain the clinical heterogeneity observed in the disease.