Evidence map›Paper›PMID 35468877›Full record

ArticleCell death & disease2022

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment.

Manman Zhang, Wenliang Gong, Dianjun Zhang, Ming Ji, Binjie Chen, Beina Chen, Xinyu Li, Yuefei Zhou, Chengyi Dong, Gehua Wen and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

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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

20 authors at 3 institutions in 4 countries.

Manman Zhang *Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Wenliang Gong *Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Dianjun Zhang *Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Ming JiDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Binjie ChenDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Beina ChenDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Xinyu LiDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Yuefei ZhouDepartment of Orthopaedics, The First Hospital, China Medical University, Shenyang, People's Republic of China.
Chengyi DongDepartment of Orthopaedics, The First Hospital, China Medical University, Shenyang, People's Republic of China.
Gehua WenDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Xiaoni ZhanDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Xiafang WuDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Lulu CuiDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Yuliang FengDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Siman WangDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Huiya YuanDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Enyu XuDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China.
Maosheng XiaDepartment of Orthopaedics, The First Hospital, China Medical University, Shenyang, People's Republic of China.
Alexei VerkhratskyDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China. Alexej.Verkhratsky@manchester.ac.uk.ORCID 0000-0003-2592-9898
Baoman LiDepartment of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang, China. bmli@cmu.edu.cn.ORCID 0000-0002-3959-9570
China Medical University · CNFirst Hospital of China Medical University · CNUniversity of Manchester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.

Indexed as

Alzheimer DiseaseCognitive DysfunctionExosomesAgedAgingAnimalsApolipoprotein E4BrainHumansLiverMiceThyroid GlandApolipoprotein E4

Identifiers

PMID35468877
PMCPMC9039072
OpenAlexW4224326428

What OpenQuestion 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 OpenQuestion graph.