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Ovariectomy and High Fat-Sugar-Salt Diet Induced Alzheimer's Disease/Vascular Dementia Features in Mice

  • 0Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Aging and Disease +

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June 24, 2024

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June 24, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers developed a new mouse model for Alzheimer's disease (AD) that mimics non-familial, late-onset AD (LOAD) by combining ovariectomy and a high-fat, high-sugar, high-salt diet, showing AD pathology and cognitive decline.

Area Of Science

  • Neuroscience
  • Pathology
  • Animal Models

Background

  • Most Alzheimer's disease (AD) is non-familial, yet common animal models represent familial forms.
  • Existing models do not fully recapitulate the environmental and metabolic factors contributing to late-onset Alzheimer's disease (LOAD).

Purpose Of The Study

  • To create a novel animal model for sporadic, non-familial Alzheimer's disease (AD) that mirrors human LOAD.
  • To investigate the combined effects of accelerated aging and metabolic risk factors on AD pathogenesis.

Main Methods

  • Naïve female mice underwent ovariectomy (OVX) to simulate menopause and accelerated aging.
  • Mice were fed a diet high in fat, sugar, and salt to induce metabolic and vascular changes.
  • Evaluated metabolic homeostasis, AD-related brain pathology, neuroinflammation, vascular integrity, and cognitive function.

Main Results

  • OVX mice on the high-risk diet exhibited metabolic dysregulation (glucose, insulin, lipids) and increased body weight.
  • These mice developed hallmark AD pathologies, including amyloid and tau tangles, alongside neuroinflammation (gliosis).
  • Impaired cerebral blood vessel density and cognitive deficits were observed, mimicking aspects of LOAD and vascular damage.

Conclusions

  • This OVX, high-risk diet mouse model effectively replicates key features of sporadic, non-familial Alzheimer's disease (AD) with concurrent vascular pathology.
  • The model provides a valuable tool for studying the pathogenesis of LOAD and for developing targeted therapeutic strategies.
  • This model's ability to recapitulate both AD and vascular pathology is crucial, as this combination is common in human dementia.