Evidence map›Paper›PMID 25642732›Full record

ArticleACS chemical neuroscience2015

Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

Shilpy Dixit, Alexandra Bernardo, Jennifer Michelle Walker, John Andrew Kennard, Grace Youngeun Kim, Eric Sean Kessler, Fiona Edith Harrison

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
8.3field-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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Infection and immunity · 2026
    Review
  4. Review
  5. Insulin resistance: fueling oxidative stress and neurodegeneration.Journal of neural transmission (Vienna, Austria : 1996) · 2025
    Review
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  7. Article
  8. Review
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  10. Article
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  14. Article
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  17. Sulfur-bridging the gap: investigating the electrochemistry of novel copper chelating agents for Alzheimer's disease applications.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023
    Article
  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Shilpy Dixit†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Alexandra Bernardo†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Jennifer Michelle Walker†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
John Andrew Kennard†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Grace Youngeun Kim†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Eric Sean Kessler†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Fiona Edith Harrison†Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
Vanderbilt University Medical Center · USVanderbilt University · US

Funding

Vitamin C and cognition in Alzheimer's diseaseR01AG038739 · NIA · VANDERBILT UNIVERSITY · PI HARRISON, FIONA EDITH · 2011 to 2014
$1.1M
NIA NIH HHS R01 AG038739
6 · The paper itself

Abstract

Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAnxietyAscorbic AcidAscorbic Acid DeficiencyBrainCognition DisordersDisease Models, AnimalFemaleLearningMaleMemoryMice, TransgenicAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid beta-Protein PrecursorAPP protein, humanAscorbic AcidPeptide FragmentsPresenilin-1PSEN1 protein, humanSlc23a2 protein, mouseSodium-Coupled Vitamin C TransportersAlzheimer’s diseaseamyloidcognitionmouse modelsoxidative stressVitamin C

Identifiers

PMID25642732
PMCPMC4476071
OpenAlexW2087448165

What OpenQuestion holds

Textmetadata
LicenceTDM
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.