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

Cristina Carvalho, Nuno Machado, Paula C. Mota, Sónia C. Correia, Susana Cardoso, Renato X. Santos, Maria S. Santos, Catarina R. Oliveira, Paula I. Moreira (Corresponding Author)

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68 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)623-635
Number of pages13
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 6 May 2013

Bibliographical note

The authors’ work is supported by the Fundacao para a Ciencia e aTecnologia co-funded by Fundo Europeu para o Desenvolvimento Regional (PTDC/SAUNEU/103325/2008) via Programa Operacional Factores de Competitividade, and Quadro de Referencia Estrategico Nacional (QREN DO-IT). C.C. has a PhD fellowship from FCT (SFRH/BD/43965/2008).
We thank Dr. Rodrigo Cunha and Dr. Joao Ramalho Santos from the Center for Neuroscience and Cell Biology, University of Coimbra, for their support with behavioral and microscopy studies.
We also thank Drs. Cristina Sena and Rosa Fernandes, from the Faculty of Medicine, University of Coimbra, for their help with Evans blue assay.
Authors’ disclosures available online http://www.jalz.com/disclosures/view.php?id=1677).


  • Alzheimer's disease
  • brain vasculature
  • behavior and cognitive function
  • mitochondria
  • type 2 diabetes


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