Evidence map›Paper›PMID 35833836›Full record

ArticleBrain : a journal of neurology2023

Extracellular vesicle biomarkers for cognitive impairment in Parkinson's disease.

Joseph Blommer, Toni Pitcher, Maja Mustapic, Erden Eren, Pamela J Yao, Michael P Vreones, Krishna A Pucha, John Dalrymple-Alford, Reza Shoorangiz, Wassilios G Meissner and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 4 pooled it
10.5field-weighted citation impact, top 1% 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

54 citing papers in PubMed, 4 syntheses or guidelines pooled it, 88 citations in OpenAlex.

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  14. Expanding the understanding of insulin resistance in brain and periphery.Trends in endocrinology and metabolism: TEM · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Joseph BlommerNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.ORCID 0000-0002-5551-9219
Toni PitcherNew Zealand Brain Research Institute, Christchurch 8011, New Zealand.
Maja MustapicNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
Erden ErenNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
Pamela J YaoNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
Michael P VreonesNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
Krishna A PuchaNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
John Dalrymple-AlfordNew Zealand Brain Research Institute, Christchurch 8011, New Zealand.
Reza ShoorangizNew Zealand Brain Research Institute, Christchurch 8011, New Zealand.
Wassilios G MeissnerNew Zealand Brain Research Institute, Christchurch 8011, New Zealand.
Tim AndersonNew Zealand Brain Research Institute, Christchurch 8011, New Zealand.
Dimitrios KapogiannisNational Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.ORCID 0000-0003-2181-3118
National Institute on Aging · USNew Zealand Brain Research Institute · NZCentre National de la Recherche Scientifique · FRUniversity of Canterbury · NZ

Funding

Studies in Dementia and Neurodegenerative DiseasesZIAAG000975 · NIA · NATIONAL INSTITUTE ON AGING · PI KAPOGIANNIS, DIMITRIOS · 2009 to 2025
$31.5M
Extraceullar Vesicle Biomarkers for Prediction of Cognitive Decline, Ab and TAU Accumulation, and atrophy in Preclinical Alzheimer's DiseaseZIAAG000003 · NIA · NATIONAL INSTITUTE ON AGING · PI KAPOGIANNIS, DIMITRIOS · 2022 to 2025
$4.4M
Brain Research New ZealandLottery Health ResearchNew Zealand Health Research CouncilNIH HHS
6 · The paper itself

Abstract

Besides motor symptoms, many individuals with Parkinson's disease develop cognitive impairment perhaps due to coexisting α-synuclein and Alzheimer's disease pathologies and impaired brain insulin signalling. Discovering biomarkers for cognitive impairment in Parkinson's disease could help clarify the underlying pathogenic processes and improve Parkinson's disease diagnosis and prognosis. This study used plasma samples from 273 participants: 103 Parkinson's disease individuals with normal cognition, 121 Parkinson's disease individuals with cognitive impairment (81 with mild cognitive impairment, 40 with dementia) and 49 age- and sex-matched controls. Plasma extracellular vesicles enriched for neuronal origin were immunocaptured by targeting the L1 cell adhesion molecule, then biomarkers were quantified using immunoassays. α-Synuclein was lower in Parkinson's disease compared to control individuals (P = 0.004) and in cognitively impaired Parkinson's disease individuals compared to Parkinson's disease with normal cognition (P < 0.001) and control (P < 0.001) individuals. Amyloid-β42 did not differ between groups. Phosphorylated tau (T181) was higher in Parkinson's disease than control individuals (P = 0.003) and in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P < 0.001) and controls (P < 0.001). Total tau was not different between groups. Tyrosine-phosphorylated insulin receptor substrate-1 was lower in Parkinson's disease compared to control individuals (P = 0.03) and in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P = 0.02) and controls (P = 0.01), and also decreased with increasing motor symptom severity (P = 0.005); serine312-phosphorylated insulin receptor substrate-1 was not different between groups. Mechanistic target of rapamycin was not different between groups, whereas phosphorylated mechanistic target of rapamycin trended lower in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P = 0.05). The ratio of α-synuclein to phosphorylated tau181 was lower in Parkinson's disease compared to controls (P = 0.001), in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P < 0.001) and decreased with increasing motor symptom severity (P < 0.001). The ratio of insulin receptor substrate-1 phosphorylated serine312 to insulin receptor substrate-1 phosphorylated tyrosine was higher in Parkinson's disease compared to control individuals (P = 0.01), in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P = 0.02) and increased with increasing motor symptom severity (P = 0.003). α-Synuclein, phosphorylated tau181 and insulin receptor substrate-1 phosphorylated tyrosine contributed in diagnostic classification between groups. These findings suggest that both α-synuclein and tau pathologies and impaired insulin signalling underlie Parkinson's disease with cognitive impairment. Plasma neuronal extracellular vesicles biomarkers may inform cognitive prognosis in Parkinson's disease.

Indexed as

Alzheimer DiseaseCognitive DysfunctionInsulinsParkinson Diseasealpha-SynucleinAmyloid beta-PeptidesBiomarkersHumansReceptor, Insulintau Proteinsalpha-SynucleinAmyloid beta-PeptidesBiomarkersInsulinsReceptor, Insulintau Proteinsbiomarkersextracellular vesiclesinsulin signallingParkinson’s diseasesynucleintau

Identifiers

PMID35833836
PMCPMC10060702
OpenAlexW4285387997

What OpenQuestion holds

Textmetadata
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.