Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies

J Alzheimers Dis. 2013;35(3):623-35. doi: 10.3233/JAD-130005.

Abstract

Type 2 diabetes (T2D) is considered a major risk factor for Alzheimer's disease (AD). To elucidate the links between both pathological conditions, we compared behavioral and cognitive functions, cerebral amyloid-β peptide (Aβ) levels and vasculature integrity of 11-month-old T2D and AD mice. For this purpose, we performed behavioral tests (open field, object recognition, Y-maze, and elevated plus maze tests), ELISA to assess plasma markers of endothelial/vascular dysfunction, spectrophotometric assays to evaluate cerebral vascular permeability and enzymatic activities, and immunohistochemistry for the assessment of Aβ levels. Both T2D and AD showed similar behavioral and cognitive anomalies characterized by increased fear and anxiety and decreased learning and memory abilities. Interestingly, both groups of animals presented increased plasma markers of endothelial/vascular dysfunction and permeability of cerebral vasculature and impaired mitochondrial enzymatic activities. In addition, a significant increase in Aβ levels was observed in the cortex and hippocampus of T2D mice. These results support the notion that T2D predisposes to cerebrovascular alterations, cognitive decline, and development of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism*
  • Amyloidosis / diagnosis
  • Amyloidosis / pathology
  • Amyloidosis / physiopathology
  • Animals
  • Behavior, Animal / physiology*
  • Brain / pathology
  • Cerebral Amyloid Angiopathy / diagnosis*
  • Cerebral Amyloid Angiopathy / pathology
  • Cerebral Amyloid Angiopathy / physiopathology
  • Cognition / physiology*
  • Diabetes Mellitus, Experimental / diagnosis*
  • Diabetes Mellitus, Experimental / parasitology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Male
  • Mice
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / pathology

Substances

  • Amyloid beta-Peptides