Cited by 98Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice

Kurata, Tomoko, Miyazaki, Kazunori, Kozuki, Miki, Panin, Violeta-Lukic, Morimoto, Nobutoshi, Ohta, Yasuyuki, Nagai, Makiko, Ikeda, Yoshio +2 more·2011·Brain Research

Abstract

In addition to simply reducing the serum level of cholesterol, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have various pleiotrophic effects such as reducing oxidative stress, neuroinflammation, and neurotoxicity. However, such a pleiotrophic effect has not been fully studied in a new statin (pitavastatin). We examined and compared the effects of two strong statins (atorvastatin, 30 mg/kg/day, p.o.; pitavastatin, 3mg/kg/day, p.o.) on the serum level of lipids, cognitive dysfunction, senile plaque (SP) and phosphorylated tau-positive dystrophic neuritis (pτDN) in amyloid precursor protein (APP) transgenic (Tg) mice from 5 months (M) of age to 20 M. These two statins improved behavioral memory and reduced the numbers of SP and pτDN at 15 and 20 M without affecting serum lipid levels, but preserved mice brain weight in pitavastatin group at 20 M. These protective effects of statins took 10 M from the beginning of treatment to show an improvement in the present model mice, and sensitivity to the statin treatment was linked to behavioral memory, SP and pτDN in this order. These findings suggest that early treatment with both atorvastatin and pitavastatin prevented subsequent worsening of cognitive function and the amyloidogenic process, probably due to pleiotrophic effects, suggesting a therapeutic potential for Alzheimer's disease (AD).

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Crossref · 10.1016/j.brainres.2010.11.067

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  • APP mouse models of AD demonstrate cognitive decline with pathology comprising Aβ plaques closely associated with areas of high oxidative stress and dystrophic neurites.

    “APP mouse models of AD demonstrate cognitive decline with pathology, comprising Aβ plaques closely associated with areas of high oxidative stress and dystrophic neurites [14,15].”

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Authors
Kurata, T., Miyazaki, K., Kozuki, M., Panin, V.-L., Morimoto, N., Ohta, Y., Nagai, M., Ikeda, Y., Matsuura, T., & Abe, K.
Affiliations
Okayama University (JP)
Corresponding author
Abe, Koji
Venue
Brain Research
Publisher
Elsevier BV
Published
2011-01
Volume
1371
Pages
161-170
ISSN
0006-8993 (ISSN-L)
OpenAlex
W2044456875
Cited by
98
References
32
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 1 · 2020: 5 · 2019: 9 · 2018: 1 · 2017: 4 · 2016: 11 · 2015: 4 · 2014: 10 · 2013: 9 · 2012: 12
FWCI
7.15
Type
journal article
Language
en
Open access
closed
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Health, Labour and Welfare
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
atorvastatin, pitavastatin, statins, Alzheimer's disease, amyloid precursor protein transgenic mice, amyloid plaques, phosphorylated tau, dystrophic neurites, cognitive function, memory, amyloidosis, neuroprotection
MeSH terms
Atorvastatin, Aging, Alzheimer Disease, Animals, Body Weight, Brain, Cognition Disorders, Female, Heptanoic Acids, Humans, Lipids, Mice, Transgenic, Organ Size, Phosphorylation, Protein Processing, Post-Translational, Pyrroles, Quinolines, Amyloid beta-Protein Precursor, tau Proteins, Neuroprotective Agents, Maze Learning, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Mice, Plaque, Amyloid

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