Evidence map›Paper›PMID 40524252›Full record

ArticleMolecular neurodegeneration2025

Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy.

Rowan Saloner, Kaitlin B Casaletto, Sruti Rayaprolu, Louisa Cornelis, Paramita Chakrabarty, Jose F Abisambra, Salvatore Spina, Lea T Grinberg, William W Seeley, Bruce L Miller and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

13 authors.

Rowan SalonerDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA. Rowan.Saloner@ucsf.edu.
Kaitlin B CasalettoDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
Sruti RayaproluDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, 1275 Center Drive, Gainesville, FL, USA.
Louisa CornelisDepartment of Physics, University of California, Broida Hall, Santa Barbara, CA, 93106, USA.
Paramita ChakrabartyDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, 1275 Center Drive, Gainesville, FL, USA.
Jose F AbisambraDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, 1275 Center Drive, Gainesville, FL, USA.
Salvatore SpinaDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
Lea T GrinbergDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
William W SeeleyDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
Bruce L MillerDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
Joel H KramerDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
Gil D RabinoviciDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, USA.
Breton M AskenDepartment of Clinical and Health Psychology, 1Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, FL, USA. basken8@phhp.ufl.edu.

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
Mechanisms of Executive Decline in Normal AgingR01AG032289 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kaitlin B Casaletto, JOEL H KRAMER · 2009 to 2026
$8.3M
Unraveling the intersection of synaptic biology, lifestyle, and cognitive resilienceR01AG072475 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CASALETTO, KAITLIN B · 2021 to 2025
$4.3M
Effects of chronic inflammation on brain structure and functionR01AG048234 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRAMER, JOEL H · 2015 to 2019
$3.2M
Alzheimer's Association AARF-23-1145318Larry L. Hillblom Foundation 2014-A-004-NETNIA NIH HHS P01 AG019724NIA NIH HHS P01AG019724NIA NIH HHS P30 AG062422NIA NIH HHS P30AG062422NIA NIH HHS P50 AG023501NIA NIH HHS R01AG032289NIA NIH HHS R01 AG048234NIA NIH HHS R01AG072475
6 · The paper itself

Abstract

backgroundExposure to repetitive head impacts (RHI) is associated with increased risk for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, and other neuropathological changes. Biological drivers of RHI-related neurodegeneration are not well understood. We interrogated the plasma proteome in aging adults with prior RHI compared to healthy controls (CTL) and individuals with Alzheimer's disease (AD), including a subset characterized neuropathologically at autopsy.

methodsProximity extension assay (Olink Explore®) quantified 2,779 plasma proteins in 22 RHI patients (all AD-biomarker negative), 39 biomarker-confirmed AD, and 44 CTL. A subset of participants went to autopsy (N = 16) allowing for comparisons of the antemortem plasma proteome between autopsy-confirmed CTE + (N = 7) and CTE- (N = 9). Differential abundance and co-expression network analyses identified plasma proteomic signatures of RHI, which were functionally annotated using gene ontology and cell type enrichment analysis. Nonparametric correlations examined plasma proteomic associations with orthogonally-measured plasma biomarkers, global cognitive function, and semi-quantitative ratings of neuropathology burden at autopsy.

resultsDifferential abundance analysis revealed 434 increased (vs. 6 decreased) proteins in RHI vs. CTL and 193 increased (vs. 14 decreased) in RHI vs. AD. Network analysis identified 9 protein co-expression modules (M1-M9), of which 7 were elevated in RHI compared to AD or CTL. Modules with increased abundance in RHI were enriched for mitochondrial/metabolic, cell division, and immunovascular (e.g., cell adhesion, TNF-signaling) processes. RHI-related modules exhibited strong and selective correlations with immunoassay-based plasma IL-6 in RHI cases, including the M2 TNF-signaling/cell adhesion module which harbored proteins that strongly tracked with cognitive function. RHI-related plasma protein signatures were similar in the subset of participants with autopsy-confirmed CTE, including immune and metabolic modules that positively correlated with medial temporal lobe tau and TDP-43 burden.

conclusionsMolecular pathways in plasma most consistently implicated in RHI were tied to immune response, mitochondrial function, and cell metabolism. RHI-related proteomic signatures tracked with antemortem cognitive severity and postmortem neuropathological burden, providing converging evidence for their role in disease progression. Differentially abundant proteins and co-expression modules in RHI may inform mechanisms linking RHI to increased dementia risk, thus guiding diagnostic biomarker and therapeutic development for at-risk populations.

Indexed as

Chronic Traumatic EncephalopathyProteomeAgedAged, 80 and overAlzheimer DiseaseBiomarkersFemaleHumansMaleMiddle AgedProteomicsBiomarkersProteomeAlzheimer’s diseaseBiomarkerChronic traumatic encephalopathyInflammationMixed neuropathologyPlasma proteomicsRepetitive head impactsTraumatic brain injuryTraumatic encephalopathy syndrome

Identifiers

PMID40524252
PMCPMC12168330

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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.