PXD045097

PXD045097 is an original dataset announced via ProteomeXchange.

Title	Aldehyde dehydrogenase 2 and Alzheimer’s disease pathology-cell line
Description	Mitochondrial aldehyde dehydrogenase 2 (ALDH2) rs671 variant, in which a G changes to A in the gene, causing a Glu to Lys mutation in the protein, results in a dramatic decrease in the catalytic activity of ALDH2. Population-based data are contradictory about whether ALDH2 rs671 variant increases the risk of Alzheimer’s disease (AD). The prevalence of the ALDH2 rs671 variant is 30%–50% in East Asian populations, but <5% elsewhere. Thus the National Human Brain Bank for Development and Function, the largest brain bank in East Asia, makes it feasible to explore the link between ALDH2 rs671 polymorphism and AD pathology. Here, using 329 human brains, we find that the ALDH2 rs671 variant elevates amyloid beta (Aβ) pathology, with increased plaque deposits and a higher Aβ40/42 ratio, but the overall A-variant is not an independent risk factor for AD. Aggregated Aβ pathology is ALDH2 activity-dependent. As the underlying mechanism, decreased ALDH2 activity leads to increased 4-hydroxy-2-nonenal (4-HNE) accumulation in the brain. The (R)-4-HNE enantiomer alters C99 process by adduction to residue Lys53 of C99 via Schiff-base formation, favoring Aβ40 generation in the Golgi apparatus. Furthermore, decreased ALDH2 activity impaired microglia double edged sword roles in AD brains, both lowered inflammatory factor secretion, as well as Aβ phagocytosis and spreading. We thus clearly define the relationship between ALDH2 rs671 polymorphism and AD, and found ALDH2 rs671 as a key regulator of Aβ40 or Aβ42 generation.
HostingRepository	iProX
AnnounceDate	2023-09-05
AnnouncementXML	Submission_2025-06-29_22:52:45.782.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wei Ge
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	TMT6plex reporter fragment
Instrument	Orbitrap Fusion Lumos; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-04 22:27:01	ID requested
⏵ 1	2025-06-29 22:52:46	announced

Dataset with its publication pending

submitter keyword: aldehyde dehydrogenase, ALDH2, rs671 polymorphism, Aβ pathology, Aβ40/42 ratio, (R)-4-HNE, 4-hydroxy-2-nonenal, microglia

Wei Ge
contact affiliation	Institute of Basic Medical Sciences Chinese Academy of Medical Sciences
contact email	gewei@ibms.cams.cn
lab head
Wei Ge
contact affiliation	Institute of Basic Medical Sciences Chinese Academy of Medical Sciences
contact email	gewei@ibms.cams.cn
dataset submitter

iProX dataset URI