Cited by 122Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and Treatments

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Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice

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Tong, Xin-Kang, Nicolakakis, Nektaria, Fernandes, Priscilla, Ongali, Brice, Brouillette, Jonathan, Quirion, Rémi, Hamel, Edith·2009·Neurobiology of Disease

DOI 10.1016/j.nbd.2009.06.003

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Abstract

Cerebrovascular dysfunctions appear to contribute to Alzheimer's disease (AD) pathogenesis and the associated cognitive decline. Recently, it has been suggested that statins could be beneficial to AD patients independently from their cholesterol-lowering effects. Using 10 month-old amyloid precursor protein transgenic mice (APP mice), we sought to reverse cerebrovascular, neuronal and memory impairments with simvastatin (20 mg/kg/day, 8 weeks). Simvastatin improved reactivity of cerebral arteries, rescued the blood flow response to neuronal activation, attenuated oxidative stress and inflammation, and reduced cortical soluble amyloid-beta (Abeta) levels and the number of Abeta plaque-related dystrophic neurites. However, at such an advanced stage of the pathology, it failed to reduce Abeta plaque load and normalize cholinergic and memory deficits. These findings demonstrate that low-dose simvastatin treatment in aged APP mice largely salvages cerebrovascular function and has benefits on several AD landmarks, which could explain some of the positive effects of statins reported in AD patients.

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Authors: Tong, X.-K., Nicolakakis, N., Fernandes, P., Ongali, B., Brouillette, J., Quirion, R., & Hamel, E.
Affiliations: Montreal Neurological Institute and Hospital (CA)
Douglas Mental Health University Institute (CA)
ORCID: Tong, Xin-Kang
Nicolakakis, Nektaria
Fernandes, Priscilla
Brouillette, Jonathan
Venue: Neurobiology of Disease
Publisher: Elsevier BV
Published: 2009-09
Volume: 35
Issue: 3
Pages: 406-414
ISSN: 0969-9961 (ISSN-L)
DOI: 10.1016/j.nbd.2009.06.003
OpenAlex: W1988125544
Cited by: 122
References: 58
Citations by year: 2026: 2 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 11 · 2015: 5 · 2014: 14 · 2013: 7 · 2012: 13
FWCI: 9.06
Type: journal article
Language: en
Open access: green
doaj.org
Licence: cc-by-sa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neurobiology of Disease (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Canadian Institutes of Health Research (MOP-62194, MOP-84275)
Alzheimer Society
Fonds de Recherche du Québec - Santé
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: simvastatin, statins, Alzheimer's disease, cerebrovascular dysfunction, cerebral blood flow, amyloid-beta, oxidative stress, neuroinflammation, APP transgenic mice, amyloid plaques, dystrophic neurites, memory impairment, cholinergic deficit, aging
MeSH terms: Aging, Alzheimer Disease, Animals, Brain, Cerebrovascular Circulation, Disease Models, Animal, Encephalitis, Humans, Learning Disabilities, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Receptors, Cell Surface, Space Perception, Neuroimmunomodulation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Oxidative Stress, Neuroprotective Agents, Simvastatin, Mice, Plaque, Amyloid, Protease Nexins

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Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice

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