AD/PD 2022 | Hyperamylinemia in early type-2 diabetes blocks Aβ elimination in the Alzheimer’s disease brain

Evidence from histological studies has shown the presence of amylin deposition in the microvasculature of Alzheimer’s disease brains, a finding not replicated in healthy controls. Florin Despa, PhD, University of Kentucky, Lexington, KY, discusses the hypothesis that hypersecretion of amylin may influence Alzheimer’s pathogenesis by altering amyloid β (Aβ) clearance. To investigate this, APP/PS1 rats were genetically modified to express amyloid-forming human amylin and Aβ transcytosis was measured. It was demonstrated that Aβ accumulation within the perivascular space frequently co-localized with deposits of amylin in the vessel wall. Additionally, the rats showed behavioral deficits earlier than normally expected in the APP/PS1 model. Dr Despa comments on the implications of these findings, which suggest that hyperamylinemia promotes the formation of mixed amylin-Aβ deposits, blocking the transport of Aβ out of the brain. This interview took place at the AD/PD™ 2022 Conference in Barcelona, Spain.