The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice

Neuropharmacology. 2015 Jun;93:134-45. doi: 10.1016/j.neuropharm.2015.01.027. Epub 2015 Feb 7.

Abstract

Alzheimer's disease (AD) is the most common senile dementia in the world. Although important progress has been made in understanding the pathogenesis of AD, current therapeutic approaches provide only modest symptomatic relief. In this study, we evaluated the neuroprotective effect of quercetin (25 mg/kg) administration via i.p. injection every 48 h for 3 months on aged (21-24 months old) triple transgenic AD model (3xTg-AD) mice. Our data show that quercetin decreases extracellular β-amyloidosis, tauopathy, astrogliosis and microgliosis in the hippocampus and the amygdala. These results were supported by a significant reduction in the paired helical filament (PHF), β-amyloid (βA) 1-40 and βA 1-42 levels and a decrease in BACE1-mediated cleavage of APP (into CTFβ). Additionally, quercetin induced improved performance on learning and spatial memory tasks and greater risk assessment behavior based on the elevated plus maze test. Together, these findings suggest that quercetin reverses histological hallmarks of AD and protects cognitive and emotional function in aged 3xTg-AD mice.

Keywords: Alzheimer's disease; Cognitive function; Neuroprotection; Quercetin; Tauopathy; β-amyloidosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antioxidants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology*
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Gliosis / etiology
  • Gliosis / prevention & control
  • Maze Learning / drug effects
  • Mice
  • Mice, Transgenic
  • Mood Disorders / etiology
  • Mood Disorders / prevention & control*
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / pathology
  • Presenilin-1 / genetics
  • Quercetin / therapeutic use*
  • Reaction Time / drug effects
  • Reaction Time / genetics
  • tau Proteins / genetics

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Antioxidants
  • Nerve Tissue Proteins
  • Presenilin-1
  • tau Proteins
  • Quercetin