Evidence map›Paper›PMID 42244657›Full record

ArticlebioRxiv : the preprint server for biology2026

Plasma proteomics reveals divergent sex-specific senescence and bone biology signatures across neurodegenerative diseases.

Siddharth Kaipa, Ting Zhai, Sai Rama Krishna Meka, Patricia Moran-Losada, Zihuai He, Divya Channappa, Hamilton Se-Hwee Oh, Jarod Rutledge, Michael Zeineh, Anthony Agudelo and 16 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

26 authors.

Siddharth KaipaDepartment of Genetics, Stanford University, Stanford, CA, USA.
Ting ZhaiDepartment of Genetics, Stanford University, Stanford, CA, USA.
Sai Rama Krishna MekaDepartment of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, IL, USA.
Patricia Moran-LosadaDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Zihuai HeDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Divya ChannappaDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Hamilton Se-Hwee OhDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8192-7593
Jarod RutledgeDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Michael ZeinehDepartment of Radiology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-6940-9096
Anthony AgudeloDepartment of Bioengineering and Biomedical Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Ramesh NairDepartment of Genetics, Stanford University, Stanford, CA, USA.
Edward N WilsonDepartment of Genetics, Stanford University, Stanford, CA, USA.
Mounica BandelaDepartment of Bioengineering and Biomedical Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Keerthana RaghuramanDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Amal Al-RajhiDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Anika AkkirajuDepartment of Cognitive Sciences, Rice University, Houston, TX, USA.
Janet HwangDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Frank M LongoDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Veronica RamirezDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Kathleen PostonDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Nicola NerettiDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
Sundeep KhoslaKogod Center on Aging and Division of Endocrinology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-2936-4372
Michael P SnyderDepartment of Genetics, Stanford University, Stanford, CA, USA.
Tony Wyss-CorayDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0001-5893-0831
Victor W HendersonDepartment of Neurology and Neurological sciences, Stanford University, Stanford, CA, USA.
Vidyani SuryadevaraDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4081-2989

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI HENDERSON, VICTOR · 2015 to 2019
$7.9M
Resilience to Alzheimer's disease in humans with exceptional longevityR01AG057909 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BARZILAI, NIR J, ZHANG, ZHENGDONG · 2017 to 2021
$6.2M
Role of exceptional longevity genotypes in protection against frailty in agingR01AG044829 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Sofiya Milman, JOE VERGHESE · 2014 to 2026
$5.4M
Somatotropic Signaling and Resilience to Aging and Alzheimer's DiseaseR01AG061155 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI MILMAN, SOFIYA · 2019 to 2023
$4.3M
USING QUANTITATIVE TRAITS TO IDENTIFY NOVEL GENES FOR ALZHEIMERS DISEASE AND OTHER COMPLEX TRAITSRF1AG053303 · NIA · WASHINGTON UNIVERSITY · PI CLIMER, SHARLEE, CRUCHAGA, CARLOS · 2016 to 2020
$4.0M
Statistical and computational methods for integrative analysis of Alzheimer's Disease geneticsR01AG066206 · NIA · STANFORD UNIVERSITY · PI HE, ZIHUAI · 2019 to 2023
$3.5M
GENETIC MODIFIERS OF CEREBROSPINAL FLUID TREM2 IN ALZHEIMER'S DISEASERF1AG058501 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, PICCIO, LAURA · 2018 to 2018
$3.5M
The Familial Alzheimer Sequencing (FASe) ProjectU01AG058922 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2018 to 2022
$3.5M
Sex-specific Molecular Profiling to Understand Pathology and Identify Causal Genes and Drug Targets for Alzheimer's DiseaseRF1AG074007 · NIA · WASHINGTON UNIVERSITY · PI SUNG, YUNJU · 2021 to 2021
$2.7M
IDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7M
NIA NIH HHS P01 AG003991NIA NIH HHS P30 AG066515NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG044829NIA NIH HHS R01 AG057909NIA NIH HHS R01 AG061155NIA NIH HHS R01 AG066206NIA NIH HHS R01 AG072255NIA NIH HHS R56 AG044829NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG058922
6 · The paper itself

Abstract

Neurodegenerative diseases are often accompanied by systemic comorbidities, including changes in bone health, but the molecular relationship between neurodegeneration, skeletal decline, and cellular senescence remains poorly understood. In this study, we investigated sex-specific changes in circulating bone- and senescence-related proteins across the spectrum of Alzheimer's disease(AD), Lewbody dementia(LB) and Parkinson's disease(PD). Plasma proteomic profiling was performed on samples from 408 participants deeply phenotyped for neurodegenerative diseases, followed by differential protein and pathway analyses. This study reveals sex-dependent alterations in bone and senescence-related circulating proteins in AD-related, PD and LB-related neurodegenerative diseases, providing insights into the complex relationship between neurodegeneration and bone health. Several candidate proteins were also associated with established plasma neurodegeneration biomarkers, particularly pTau181. Pathway analyses revealed shared mitochondrial and metabolic dysfunction across neurodegenerative diseases, with disease-specific features including vesicle trafficking disruption in AD and inflammatory-senescence pathways in LB, plus sex-divergent patterns in inflammatory signaling and bone-related pathways.

Indexed as

agingAlzheimer’s diseasebiomarkersboneLewy body dementiaParkinson’s diseasepathway analysisProteomicssenescence

Identifiers

PMID42244657
PMCPMC13232200

What OpenQuestion holds

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Registered trials

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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.