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P2‐060: A Harmonized Protocol for Medial Temporal Lobe Subfield Segmentation: Initial Results of The 3‐Tesla Protocol For The Hippocampal Body
Author(s) -
Wisse Laura E.M.,
Daugherty Ana M.,
Amaral Robert S.C.,
Berron David,
Carr Valerie A.,
Ekstrom Arne D.,
Kanel Prabesh,
Kerchner Geoffrey A.,
Mueller Susanne G.,
Pluta John,
Stark Craig E.,
Steve Trevor,
Wang Lei,
Yassa Michael A.,
Yushkevich Paul A.,
La Joie Renaud
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1265
Subject(s) - hippocampal formation , white matter , segmentation , temporal lobe , diffusion mri , lobe , anatomy , neuroscience , magnetic resonance imaging , psychology , medicine , computer science , artificial intelligence , radiology , epilepsy
from humans, compared human amylin-expressing (HIP) rats (n1⁄415) with ageand glucose-matched diabetic rats expressing only endogenous non-amyloidogenic rat amylin (n1⁄415), studied mice injected with aggregated human amylin versus controls (n1⁄410 per group) and developed in vitro cell models. Results:LCMS/MS data convincingly demonstrated that amylin is contained in brain lysates from AD patients. In addition to amylin plaques and mixed amylin-ß amyloid deposits, brains of diabetic patients with AD show amylin immunoreactive deposits inside the neurons. Neuronal amylin formed adducts with 4-hydroxynonenal (4-HNE), a marker of peroxidative membrane injury, and increased (by 45% vs. control; P<0.001) synthesis of the proinflammatory cytokine interleukin (IL)-1ß. These pathological changes were mirrored in rats expressing human amylin in pancreatic islets (HIP rats) and mice intravenously injected with aggregated human amylin, but not in hyperglycemic rats secreting wild-type non-amyloidogenic rat amylin. In cultured primary hippocampal rat neurons, aggregated amylin increased IL-1ß synthesis via membrane destabilization and subsequent generation of 4-HNE. These effects were blocked by membrane stabilizers and lipid peroxidation inhibitors. Conclusions: Elevated blood levels of aggregated amylin can promote brain accumulation of amylin leading to peroxidative membrane injury and aberrant inflammatory responses independent of other confounding factors of diabetes. Present results are consistent with the pathological role of aggregated amylin in the pancreas, demonstrate a novel contributing mechanism to neurodegeneration and suggest a direct, potentially treatable link of type-2 diabetes with AD.