Altering ApoE in mice expressing human amylin in the pancreas exacerbates brain amyloid pathology and behavior deficits

Our data suggest ApoE may function as a transporter of amyloid-forming amylin in the brain with amylin binding ApoE4 stronger than ApoE3. The increased affinity of amylin for ApoE4 coincides with worsened brain amyloid pathology, disrupted β-amyloid homeostasis, increased astrogliosis suggesting neurodegenerative insult, and functional impairments due to elevated amylin amyloid burden. These data may implicate the amylin-ApoE interaction as a mechanism underlying ApoE4-specific neuropathology. Additional studies to delineate the mechanisms by which amylin and ApoE interact at the BBB interface and alter amyloid deposition are needed.