Cited by 580Alzheimer's disease research and treatmentsDietary Effects on HealthDementia and Cognitive Impairment Research

Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease

Open access
Halagappa, Veerendra Kumar Madala, Guo, Zhihong, Pearson, Michelle, Matsuoka, Yasuji, Cutler, Roy G., LaFerla, Frank M., Mattson, Mark P.·2007·Neurobiology of Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid beta-peptide (Abeta) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD (3xTgAD mice). Groups of 3xTgAD mice were maintained on an ad libitum control diet, or CR or IF diets, beginning at 3 months of age. Half of the mice in each diet group were subjected to behavioral testing (Morris swim task and open field apparatus) at 10 months of age and the other half at 17 months of age. At 10 months 3xTgAD mice on the control diet exhibited reduced exploratory activity compared to non-transgenic mice and to 3xTgAD mice on CR and IF diets. Overall, there were no major differences in performance in the water maze among genotypes or diets in 10-month-old mice. In 17-month-old 3xTgAD mice the CR and IF groups exhibited higher levels of exploratory behavior, and performed better in both the goal latency and probe trials of the swim task, compared to 3xTgAD mice on the control diet. 3xTgAD mice in the CR group showed lower levels of Abeta1-40, Abeta1-42 and phospho-tau in the hippocampus compared to the control diet group, whereas Abeta and phospho-tau levels were not decreased in 3xTgAD mice in the IF group. IF may therefore protect neurons against adverse effects of Abeta and tau pathologies on synaptic function. We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies.

Integrity signals

Registry

Crossref · 10.1016/j.nbd.2006.12.019

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Caloric restriction was found to reduce amyloid-β deposition and improve learning and memory in transgenic mouse models of Alzheimer's disease.

    “There is also evidence that caloric restriction may confer resistance to Alzheimer’s-disease-type pathology: caloric restriction was found to reduce amyloid-β deposition and improve learning and memory in transgenic mouse models of Alzheimer’s disease (79).”

    From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [79]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Halagappa, V. K. M., Guo, Z., Pearson, M., Matsuoka, Y., Cutler, R. G., LaFerla, F. M., & Mattson, M. P.
Affiliations
  • National Institute on Aging (US)
  • Georgetown University Medical Center (US)
  • University of California, Irvine (US)
Corresponding author
Mattson, Mark P.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2007-04
Volume
26
Issue
1
Pages
212-220
ISSN
0969-9961 (ISSN-L)
OpenAlex
W1965263019
Cited by
580
References
60
Citations by year
2026: 28 · 2025: 30 · 2024: 27 · 2023: 33 · 2022: 40 · 2021: 37 · 2020: 38 · 2019: 37 · 2018: 25 · 2017: 35 · 2016: 29 · 2015: 29 · 2014: 37 · 2013: 24 · 2012: 22
FWCI
18.11
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging (AG022455)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, intermittent fasting, caloric restriction, 3xTg-AD mice, triple transgenic mouse model, age-related cognitive decline, amyloid-beta, tau phosphorylation, hippocampus, exploratory behavior, Morris water maze, hypocaloric diet, neuroprotection
MeSH terms
Aging, Alzheimer Disease, Animals, Fasting, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Immunoblotting, Amyloid beta-Peptides, tau Proteins, Maze Learning, Caloric Restriction, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review