ArticleCell death discovery2025
APOE4 promotes nigral tau hyperphosphorylation through cholesterol in atherosclerosis.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nigral tau hyperphosphorylation has been implicated as an initiation of nigrostriatal dopaminergic neurodegeneration. Apolipoprotein epsilon 4 allele (APOE4) is a common risk factor of Parkinson's disease (PD) and atherosclerosis (AS). Whether APOE4 carriers exhibited higher levels of nigral phosphorylated tau (p-tau) and the correlation between AS- and PD-related tauopathy remain elusive. Here, the tau pathology was observed in APOE4 carried and non-APOE4 carried AS patients postmortem brain substantia nigra pars compacta (SNpc). APOE3/3 and APOE4/4 knock-in mice treated with high fat diet (APOE3-HFD and APOE4-HFD, respectively) were used to simulate AS model. The tau-related neuropathology and behavioral performances were analyzed. Postmortem brain analysis showed that APOE4-carried AS patients exhibited elevated nigral p-tau level relative to non-APOE4 carriers. APOE4 mice fed with HFD exhibited higher p-tau, cholesterol accumulation, and larger AS plaque area in contrast to APOE3-HFD. Cholesterol triggered GSK3β activation, leading to tau phosphorylation in primary cultured neurons. Aiding cholesterol transport alleviated nigral cholesterol accumulation and tau pathology, thereby mitigating the tau-mediated nigrostriatal degeneration. This alleviated degeneration might also contribute to motor function recovery. These findings showed a link between nigral dopaminergic tau-related pathology and AS phenotype, and targeting cholesterol might alleviate both PD-like tauopathy and AS.
Identifiers
What OpenQuestion holds
Registered trials
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.