Evidence map›Paper›PMID 38519490›Full record

ArticleNature communications2024

The aldehyde dehydrogenase 2 rs671 variant enhances amyloid β pathology.

Xia Wang, Jiayu Wang, Yashuang Chen, Xiaojing Qian, Shiqi Luo, Xue Wang, Chao Ma, Wei Ge

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Journal of the American Heart Association · 2026
    Article
  5. Integrated transcriptomic profiling combined withFrontiers in aging neuroscience · 2026
    Article
  6. Article
  7. AldehydeFrontiers in medicine · 2026
    Article
  8. Review
  9. Article
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

8 authors at 1 institution in 1 country.

Xia Wang *Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0002-3165-773X
Jiayu Wang *Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0009-0003-4899-9335
Yashuang ChenDepartment of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Xiaojing QianDepartment of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Shiqi LuoDepartment of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Xue WangDepartment of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Chao MaDepartment of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China. machao@ibms.cams.cn.ORCID http://orcid.org/0000-0003-1346-6961
Wei GeDepartment of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China. gewei@ibms.cams.cn.ORCID http://orcid.org/0000-0002-9907-512X
Chinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81971023National Natural Science Foundation of China (National Science Foundation of China) 82171332National Natural Science Foundation of China (National Science Foundation of China) 92353302
6 · The paper itself

Abstract

In the ALDH2 rs671 variant, a guanine changes to an adenine, resulting in a dramatic decrease in the catalytic activity of the enzyme. Population-based data are contradictory about whether this variant increases the risk of Alzheimer's disease. In East Asian populations, the prevalence of the ALDH2 rs671 variant is 30-50%, making the National Human Brain Bank for Development and Function (the largest brain bank in East Asia) an important resource to explore the link between the ALDH2 rs671 polymorphism and Alzheimer's disease pathology. Here, using 469 postmortem brains, we find that while the ALDH2 rs671 variant is associated with increased plaque deposits and a higher Aβ40/42 ratio, it is not an independent risk factor for Alzheimer's disease. Mechanistically, we show that lower ALDH2 activity leads to 4-HNE accumulation in the brain. The (R)-4-HNE enantiomer adducts to residue Lys53 of C99, favoring Aβ40 generation in the Golgi apparatus. Decreased ALDH2 activity also lowers inflammatory factor secretion, as well as amyloid β phagocytosis and spread in brains of patients with Alzheimer's disease. We thus define the relationship between the ALDH2 rs671 polymorphism and amyloid β pathology, and find that ALDH2 rs671 is a key regulator of Aβ40 or Aβ42 generation.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAldehyde DehydrogenaseAldehyde Dehydrogenase, MitochondrialGenetic Predisposition to DiseaseHumansPolymorphism, Single NucleotideAldehyde DehydrogenaseAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanAmyloid beta-Peptides

Identifiers

PMID38519490
PMCPMC10959958
OpenAlexW4393078425

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.