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Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by Intracerebroventricular Injection of Composited Amyloid Beta Protein
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Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer's disease-experimental

Jun Wang1, Weina Bi2, Alice Cheng2

  • 1Department of Neurology, Icahn School of Medicine at Mount Sinai New York, NY, USA ; Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center Bronx, NY, USA.

Frontiers in Aging Neuroscience
|March 28, 2014
PubMed

Insights

Combining grape seed extract, resveratrol, and Concord grape juice extract showed synergistic effects in mitigating Alzheimer's disease (AD) pathology and cognitive decline in mice. This multi-target polyphenol approach offers promising therapeutic potential for AD.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Gerontology

Background:

  • Alzheimer's disease (AD) is a leading cause of age-related neurodegeneration with no current cure.
  • Effective AD treatment likely requires targeting multiple pathological pathways simultaneously.
  • Polyphenols offer potential therapeutic benefits due to their known health advantages.

Purpose of the Study:

  • To investigate the synergistic effects of a combination of three polyphenolic preparations (grape seed extract, resveratrol, Concord grape juice extract) on Alzheimer's disease (AD) pathology and cognitive function.
  • To evaluate whether this combined polyphenol treatment can mitigate amyloid-beta (Aβ) mediated neuropathology and cognitive impairments in a mouse model of AD.

Main Methods:

  • Administration of a combination of three polyphenolic preparations to J20 AD mice.
  • Assessment of cognitive impairments and neuropathology, including amyloid content.
  • Electrophysiological examination of hippocampal slices to assess long-term potentiation (LTP) deficits induced by oligomeric Aβ (oAβ).

Main Results:

  • Combination polyphenol treatment demonstrated superior protection against cognitive impairments compared to individual treatments in J20 AD mice.
  • Significant reduction in total brain amyloid content was observed following combination treatment.
  • Acute treatment with brain-penetrating polyphenol metabolites improved oAβ-induced LTP deficits in hippocampal slices.

Conclusions:

  • A multi-target approach using combined polyphenols can synergistically mitigate AD neuropathology and cognitive deficits.
  • This study provides evidence for the therapeutic potential of combining polyphenols with distinct compositions and bioactivities for AD treatment.
  • Targeting multiple disease mechanisms with polyphenols may increase the likelihood of therapeutic efficacy in Alzheimer's disease.
Keywords:
Alzheimer's disease (AD)J20 micegrape juicegrape seed extractpolyphenolsresveratrol

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