Evidence mapPaperPMID 41709697Full record

ArticleBrain : a journal of neurology2026

Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD.

Maria J Lagartos-Donate, Beatriz Escobar-Doncel, Shi-Qi Zhang, Jun-Ping Pan, Noemí Villaseca González, Alexander Anisimov, Nicola P Montaldo, Vidar Jensen, Lipeng Mao, Bailei Li and 12 more

Abstract read
In one paragraph

Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Maria J Lagartos-DonateDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Beatriz Escobar-DoncelDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Shi-Qi ZhangDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Jun-Ping PanDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Noemí Villaseca GonzálezFaculty of Pharmacy and Biomedicine Institute, University of Castilla-La Mancha, Albacete 02071, Spain.
Alexander AnisimovDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Nicola P MontaldoDepartment of Microbiology, Oslo University Hospital, Oslo 0424, Norway.
Vidar JensenDepartment of Molecular Medicine, University of Oslo, Oslo 0372, Norway.
Lipeng MaoDepartment of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510632, China.
Bailei LiDepartment of Biotechnology and Biomedicine and Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing, 314006, China.
Nuria Banzon-PereiraDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Liu ShiDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
Shu-Qin CaoDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Domenica CaponioDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.
Pingjie WangDepartment of Geriatrics, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
Rajeevkumar Raveendran NairKavli Institute for Systems Neuroscience, NTNU, Trondheim 7030, Norway.
Oscar Junhong LuoDepartment of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510632, China.
Guobing ChenInstitute of Geriatric Immunology, Department of Microbiology and Immunology, School of Medicine, Jinan University, No.601, West Huangpu Avenue, Tianhe District, Guangzhou 510632, China.
Alejo J Nevado-HolgadoDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
Noel BuckleyDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.ORCID 0000-0003-1152-0653
Hilde Loge NilsenDepartment of Microbiology, Oslo University Hospital, Oslo 0424, Norway.
Evandro Fei FangDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway.

Funding

Akershus University Hospital #261973Akershus University Hospital #262960Akershus University Hospital #269901Civitan Norges Forskningsfond for Alzheimers sykdom #281931Cure Alzheimer's Fund #282952Cure Alzheimer's Fund #284930Czech Republic-Norway KAPPA programme #101073251Czech Republic-Norway KAPPA programme #TO01000215Helse Sør-Øst #2020001Helse Sør-Øst #2021021Helse Sør-Øst #2023093Molecule AG/VITADAO #282942Nasjonalforeningen for folkehelse #35590National Natural Science Foundation of China #81971327National Natural Science Foundation of China #82301422NordForsk Foundation #119986Research Council of Norway #262175Research Council of Norway #334361Wellcome Leap's Dynamic Resilience Program #104617
6 · The paper itself

Abstract

Downregulation and inactivation of the Repressor Element 1-Silencing Transcription factor (REST) is shown in Alzheimer's disease (AD) and likely contributes to its progression, but the exact molecular mechanism linking REST reduction to AD remains unclear. We examined changes in REST expression in the entorhinal cortex and hippocampus across different Braak stages of tauopathy. We show that alterations in REST expression and sub-cellular localization are partially responsible for AD pathology, as REST overexpression improves cognition, reduces amyloid-β and phosphorylated Tau deposition, and restores mitochondrial and synaptic homeostasis. Mechanistically, the NAD+/SIRT1 axis modulates REST expression through chromatin remodelling in the promoter region of REST, leading to changes in the expression of REST target genes involved in mitophagy and synaptic function. These findings reveal a new mechanism of action for NAD+ and highlight REST as a promising therapeutic target for AD therapy.

Indexed as

Alzheimer DiseaseNADRepressor ProteinsAmyloid beta-PeptidesAnimalsEntorhinal CortexFemaleHippocampusHumansMaleMiceRE1-Silencing Transcription FactorSirtuin 1tau ProteinsAmyloid beta-PeptidesNADRE1-Silencing Transcription FactorRepressor ProteinsSirtuin 1tau ProteinsAlzheimer’s diseasedementiamitophagyNAD+RESTSIRT1

Identifiers

PMID41709697
PMCPMC13058456

What Socratic holds

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Registered trials

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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.