Evidence map›Paper›PMID 22492027›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012

Age-dependent rescue by simvastatin of Alzheimer's disease cerebrovascular and memory deficits.

Xin-Kang Tong, Clotilde Lecrux, Pedro Rosa-Neto, Edith Hamel

Erratum issuedOpen access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 160 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Vascular Function and Ion Channels in Alzheimer's Disease.Microcirculation (New York, N.Y. : 1994) · 2024
    Review
  8. Review
  9. Article
  10. Behavioral and Metabolic Effects of ABCG4 KO in the APPJournal of molecular neuroscience : MN · 2024
    Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Sex modifies the relationship between age and neurovascular coupling in healthy adults.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
  17. Article
  18. Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of AβThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  19. Article
  20. Article

34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
    Rosa-Neto, Pedro [added]
5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Xin-Kang TongLaboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, Montréal, Québec H3A 2B4, Canada.
Clotilde Lecrux
Pedro Rosa-Neto
Edith Hamel
Gladstone Institutes · USMcGill University · CA

Funding

Canadian Institutes of Health Research MOP-84275
6 · The paper itself

Abstract

Alzheimer's disease (AD) is now established as a progressive compromise not only of the neurons but also of the cerebral vasculature. Increasing evidence also indicates that cerebrovascular dysfunction may be a key or an aggravating pathogenic factor in AD, emphasizing the importance to properly control this deficit when aiming for effective therapy. Here, we report that simvastatin (3-6 months, 40 mg/kg/d) completely rescued cerebrovascular reactivity, basal endothelial nitric oxide synthesis, and activity-induced neurometabolic and neurovascular coupling in adult (6 months) and aged (12 months) transgenic mice overexpressing the Swedish and Indiana mutations of the human amyloid precursor protein (AD mice). Remarkably, simvastatin fully restored short- and long-term memory in adult, but not in aged AD mice. These beneficial effects occurred without any decreasing effect of simvastatin on brain amyloid-β (Aβ) levels or plaque load. However, in AD mice with recovered memory, protein levels of the learning- and memory-related immediate early genes c-Fos and Egr-1 were normalized or upregulated in hippocampal CA1 neurons, indicative of restored neuronal function. In contrast, the levels of phospholipase A2, enkephalin, PSD-95, synaptophysin, or glutamate NMDA receptor subunit type 2B were either unaltered in AD mice or unaffected by treatment. These findings disclose new sites of action for statins against Aβ-induced neuronal and cerebrovascular deficits that could be predictive of therapeutic benefit in AD patients. They further indicate that simvastatin and, possibly, other brain penetrant statins bear high therapeutic promise in early AD and in patients with vascular diseases who are at risk of developing AD.

Indexed as

AgingAlzheimer DiseaseAnimalsCerebrovascular CirculationCerebrovascular DisordersFemaleHumansMaleMemory DisordersMiceMice, Inbred C57BLMice, TransgenicSimvastatinSimvastatin

Identifiers

PMID22492027
PMCPMC6620905
OpenAlexW1998104918

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.