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

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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Crossref · 10.1016/j.nbd.2009.06.003

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  • Concomitant BBB dysfunction reduces intracerebral transport of glucose and other nutrients and decreases removal of excess metabolites, thus altering homeostasis in the central nervous system.

    “The concomitant BBB dysfunction not only reduces the intracerebral transport of glucose and other nutrients,[ 10 ] but also decreases the removal of excess metabolites,[ 11 ] thus alters the homeostasis in the central nervous system (CNS).”

    From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [10]

  • 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].”

    From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [15]

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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
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
Licence
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
  • Health Sciences › Medicine › Physiology › 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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