Evidence mapPaperPMID 41816968Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

ALKBH3 m1A Demethylase Deficiency Reduces Alzheimer's Amyloid-β Pathology.

Yueyang Li, Sifei Yu, Kaidong Lu, Yujie Zhang, Mingjie Dong, Yan Peng, Liang Xue, Waleed Alam, Yuxuan Shui, Yi Zhou and 16 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

26 authors.

Yueyang LiPeking University, Beijing, China.
Sifei YuBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Kaidong LuBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yujie ZhangBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Mingjie DongBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yan PengPeking University, Beijing, China.
Liang XueBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Waleed AlamBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yuxuan ShuiPeking University, Beijing, China.
Yi ZhouBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Wuyunhan MaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Meng BaoBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Peiming LiBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Peiyi LuoBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Tiezhan LuBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Jiajia LiBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Kang ZhangBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yuying WangBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Shuchen YangBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Nuoya YinState Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
Francesco FaiolaState Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
Zilong GaoBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Jingfeng ZhouBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Fei ZhaoBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yali HeBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Magdalena J KoziolBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0002-4123-4343

Funding

Beijing Natural Science Foundation IS23091Beijing Postdoctoral Research Foundation Fellowship 2020-YJ-002Beijing Postdoctoral Research Foundation Fellowship 2022-ZZ-005Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences 2019-I2M-5-015
6 · The paper itself

Abstract

Amyloid-beta (Aβ) aggregation, mitochondrial dysfunction, and cognitive decline are hallmarks of Alzheimer's disease (AD), but its initiating molecular events remain unknown. Given that RNA modifications regulate neurodevelopment and neurodegeneration, we explore their functional role in 5xFAD mice, an Aβ AD model. We discover that N1-methyladenosine (m1A) is the most altered RNA modification, and that its regulator demethylase, ALKBH3 is upregulated. Strikingly, Alkbh3 reduction decreases Aβ plaques and restores cognition. Conversely, elevated ALKBH3 levels, observed in AD patients, compromise neuronal morphology and mitochondrial function by impairing mitophagy (degradation of dysfunctional mitochondria), a known driver of neuronal dysfunction. Mechanistically, we reveal that ALKBH3 removes m1A from PINK1 mRNA, the mitophagy master regulator. Given that ALKBH3 is elevated in human AD, causally linked to mitophagy impairment, and confers neuroprotection when depleted, we present ALKBH3 as a mechanistically validated therapeutic target in AD.

Indexed as

AlkB Homolog 3, Alpha-Ketoglutarate-Dependent DioxygenaseAlzheimer DiseaseAmyloid beta-PeptidesAnimalsDisease Models, AnimalHumansMiceMice, TransgenicMitochondriaMitophagyPTEN-Induced Putative KinaseRNA MethylationALKBH3 protein, humanAlkB Homolog 3, Alpha-Ketoglutarate-Dependent DioxygenaseAmyloid beta-PeptidesPTEN-Induced Putative KinaseALKBH3Alzheimer's disease (AD)Amyloid‐β, m1Amitochondrialmitophagy

Identifiers

PMID41816968
PMCPMC13252633

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.