Basic Science and Pathogenesis.

Background: The APOE ε4 allele is the most prominent genetic predisposition for sporadic Alzheimer's disease (AD). Amylin, a neuroendocrine hormone co-secreted with insulin from the pancreas, is increased in blood in AD and readily forms neurotoxic homo- and hetero-oligomers with β-amyloid in AD. Previously, we showed that intravenously infused ApoE4 in rats expressing human amylin specifically in the pancreas led to increased brain amylin accumulation.

Basic Science and Pathogenesis.

Background: Impaired interstitial fluid drainage in the brain is indicated by the presence of perivascular β-amyloid (Aβ) deposits and is attributed to alterations in contractility and relaxation of vascular smooth muscle cells (SMCs). The brain microvasculature in Alzheimer disease (AD) accumulates amyloid-forming amylin secreted from the pancreas. Here, we tested the hypothesis that cerebrovascular amylin deposits perturbs cerebral Aβ efflux by impairing cerebral vasodilation.

Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis.

Amylin is a systemic neuroendocrine hormone co-expressed and co-secreted with insulin by pancreatic β-cells. In persons with thype-2 diabetes, amylin forms pancreatic amyloid triggering inflammasome and interleukin-1β signaling and inducing β-cell apoptosis. Here, we summarize recent progress in understanding the potential link between amyloid-forming pancreatic amylin and Alzheimer's disease (AD).