Evidence map›Paper›PMID 42786742›Full record

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

TMEM59 regulates microglial Aβ phagocytosis in a TREM2-dependent manner and acts as a potential therapeutic target for Aβ amyloidosis.

Jian Meng, Yong Wang, Jinghui Wang, Yiqing Chen, Zihao Zhao, Ziqian Tang, Jing Cao, Xian Zhang, Hong Luo, Huihui Li and 4 more

Abstract read
PubMed Full text at PMC Publisher
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.

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

14 authors.

Jian Meng *Xiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Yong Wang *Xiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Jinghui Wang *Xiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Yiqing ChenXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Zihao ZhaoXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Ziqian TangXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Jing CaoXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Xian ZhangXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Hong LuoXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Huihui LiXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Yili WuCenter for Geriatric Medicine, International Center for Alzheimer's Research, Prevention and Treatment, Oujiang Laboratory, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yingjun ZhaoXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Weihong SongCenter for Geriatric Medicine, International Center for Alzheimer's Research, Prevention and Treatment, Oujiang Laboratory, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yun-Wu ZhangXiamen Key Laboratory of Brain Center, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.ORCID https://orcid.org/0000-0002-7152-7630

Funding

Changping Laboratory 2025B-07-39China Postdoctoral Science Foundation 2025M782230National Natural Science Foundation of China 82371420National Natural Science Foundation of China 82501698National Natural Science Foundation of China 82588301National Natural Science Foundation of China U25A2072
6 · The paper itself

Abstract

introductionMicroglia-mediated clearance of amyloid beta (Aβ) is crucial for mitigating Alzheimer's disease (AD) progression, yet the molecular regulators of microglial phagocytosis remain incompletely understood.

methodsWe assessed AD-related phenotypes in 5xFAD mice with microglia-specific deletion of transmembrane protein 59 (TMEM59). Microglial transcriptomic profiling was performed using single-cell RNA sequencing (scRNA-seq). A chaperone-mediated autophagy-targeting chimera (CMATAC) peptide was developed to degrade TMEM59, and its therapeutic efficacy was evaluated.

resultsMicroglia-specific TMEM59 ablation attenuated cognitive deficits, Aβ plaque burden, and synapse loss in 5xFAD mice. TMEM59 deficiency reprogrammed disease-associated microglia toward a highly phagocytic state. Mechanistically, TMEM59 deficiency enhanced microglial Aβ phagocytosis in a triggering receptor expressed on myeloid cells 2 (TREM2)-dependent manner, as it stabilized TREM2 protein, whereas loss of TREM2 abolished these protective effects. Treatment with the TMEM59-degrading CMATAC peptide alleviated behavioral deficits and enhanced microglial Aβ phagocytosis in 5xFAD mice. DISCUSSION: TMEM59 is a key regulator of microglial phagocytosis in AD and a novel target for amyloidosis intervention.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloidosisMembrane GlycoproteinsMembrane ProteinsMicrogliaNerve Tissue ProteinsPhagocytosisReceptors, ImmunologicAnimalsDisease Models, AnimalMiceMice, TransgenicPlaque, AmyloidAmyloid beta-PeptidesMembrane GlycoproteinsMembrane ProteinsNerve Tissue ProteinsReceptors, ImmunologicTmem59 protein, mouseTrem2 protein, mouseAlzheimer's diseaseamyloidchaperone‐mediated autophagy‐targeting chimeramicrogliaphagocytosisTMEM59transmembrane protein 59TREM2triggering receptor expressed on myeloid cells 2

Identifiers

PMID42786742
PMCPMC13612970

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.