Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease

Ramon Velazquez, An Tran, Egide Ishimwe, Larry Denner, Nikhil Dave, Salvatore Oddo, Kelly Dineley

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We report that CNS insulin signaling abnormalities are evident months before peripheral insulin resistance. In addition, we find that brain energy metabolism is differentially altered in both mouse models, with 3xTg-AD mice showing more extensive changes. Collectively, our data suggest that early AD may reflect engagement of different signaling networks that influence CNS metabolism, which in turn may alter peripheral insulin signaling.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalNeurobiology of Aging
Volume58
DOIs
StatePublished - Oct 1 2017

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Alzheimer Disease
Insulin
Insulin Resistance
Central Nervous System
Vascular Resistance
Metabolic Diseases
Hyperglycemia
Neurodegenerative Diseases
Energy Metabolism
Homeostasis
Chronic Disease
Animal Models
Glucose
Brain

Keywords

  • 3xTg-AD
  • Aging
  • Alzheimer's disease
  • Energy metabolism
  • Glucose tolerance test
  • Insulin resistance
  • Neurodegeneration
  • Tg2576
  • Type two diabetes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease. / Velazquez, Ramon; Tran, An; Ishimwe, Egide; Denner, Larry; Dave, Nikhil; Oddo, Salvatore; Dineley, Kelly.

In: Neurobiology of Aging, Vol. 58, 01.10.2017, p. 1-13.

Research output: Contribution to journalArticle

Velazquez, Ramon ; Tran, An ; Ishimwe, Egide ; Denner, Larry ; Dave, Nikhil ; Oddo, Salvatore ; Dineley, Kelly. / Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease. In: Neurobiology of Aging. 2017 ; Vol. 58. pp. 1-13.
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