Cintron A, Rosen R, Ciliax B, Walker L, LeVine III H.
PIB Binding in APP-Transgenic Mice Exogenously Seeded with AD-brain Extract.
Human Amyloid Imaging Abstract. 2012 Jan 1;
The misfolding and aggregation of β-amyloid (Aβ) is one of the earliest events in the pathogenesis of Alzheimer’s disease. The induction and spread of these lesions may involve corruptive protein templating (seeding), similar to the molecular mechanism underlying prion disease. Experimentally, Aβ deposition can be induced in Aβ-precursor protein- (APP) transgenic mice by the intracerebral injection of dilute brain extracts that contain misfolded, aggregated Aβ seeds. Radiolabeled Pittsburgh compound B (PIB) binds with high affinity and specificity to cerebral Aβ deposits in patients with Alzheimer’s disease. However, PIB high-affinity binding sites are very rare on Aβ deposits in APP-transgenic mice and aged nonhuman primates, even though these models express human-sequence Aβ. We asked whether high-affinity PIB binding sites can be generated on Aβ deposits that have been seeded by AD-brain extracts in APP-transgenic mice. Using autoradiography of HPIB binding to tissue sections, we found that PIB binding is augmented in seeded deposits of Aβ in this model, suggesting that the seed can influence the characteristics of the resulting protein aggregates in vivo. Establishing an understanding of corruptive protein templating and the strain-like features of Aβ structure in Alzheimer’s disease will provide new insights into the characteristics of proteopathic lesions that are specific to Alzheimer’s disease.