Evidence mapPaperPMID 41830497Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Late-life methionine restriction attenuates neuroinflammation in Alzheimer's disease mice via FGF21 activation in a metabolism-independent manner.

Yuyu Zhang, Yiju Li, Qianxu Wang, Jingxi Pang, Da Wang, Tian Yuan, Zhigang Liu

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yuyu ZhangLaboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Yiju LiAgriculture/Forestry Centre, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Qianxu WangLaboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Jingxi PangLaboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Da WangLaboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Tian YuanShaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, China.
Zhigang LiuLaboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.

Funding

Basic Research Project of Shenzhen Natural Science Foundation JCYJ20220530161401004Basic Research Project of Shenzhen Natural Science Foundation JCYJ20230807111402005National Natural Science Foundation of China 32241012National Natural Science Foundation of China 81871118Sci-Tech Innovation 2030 Brain Science and Brain-Like Intelligence Technology 2022ZD0208100
6 · The paper itself

Abstract

introductionAging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and may protect brain function, but its efficacy and mechanisms when started late are unclear.

methodsFourteen-month-old male APP/PS1 mice received 17 weeks of MR (0.17% methionine); behavioral, histological, and molecular assays were performed and hippocampal FGFR1 was knocked down by adeno-associated virus.

resultsLate-life MR improved peripheral glucose/lipid profiles, reduced Aβ deposition, preserved synaptic markers, and suppressed neuroinflammation. MR-induced hepatic FGF21 and brain FGFR1-AMPKα signaling to inhibit NFκB; hippocampal FGFR1 knockdown abolished MR's neuroprotective effects while leaving peripheral metabolic changes intact. DISCUSSION: Even when initiated in late life, MR robustly reduces AD pathology via the hepatic FGF21-brain FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21-FGFR1 axis as actionable late-life intervention targets with potential for clinical translation.

Indexed as

Alzheimer DiseaseFibroblast Growth FactorsMethionineNeuroinflammatory DiseasesAnimalsBrainDisease Models, AnimalHippocampusMaleMiceMice, TransgenicReceptor, Fibroblast Growth Factor, Type 1fibroblast growth factor 21Fibroblast Growth FactorsMethionineReceptor, Fibroblast Growth Factor, Type 1Alzheimer's Diseasefibroblast growth factor 21metabolismmethionine restrictionneuroinflammation

Identifiers

PMID41830497
PMCPMC13093841

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.