Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context
Summary: Background: The simultaneous memory and gait decline is linked to greater dementia risk than memory decline alone. We aim to identify dual decline-related protein changes that may offer valuable insights into biological processes. Methods: We compared longitudinal changes in 7268 plasma pr...
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Elsevier
2025-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425003020 |
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| author | Qu Tian Erin E. Greig Michael R. Duggan Keenan A. Walker Luigi Ferrucci |
| author_facet | Qu Tian Erin E. Greig Michael R. Duggan Keenan A. Walker Luigi Ferrucci |
| author_sort | Qu Tian |
| collection | DOAJ |
| description | Summary: Background: The simultaneous memory and gait decline is linked to greater dementia risk than memory decline alone. We aim to identify dual decline-related protein changes that may offer valuable insights into biological processes. Methods: We compared longitudinal changes in 7268 plasma proteomic markers in older adults experiencing dual decline, memory decline, and gait decline from no decline (reference) using linear mixed-effects regression and related to brain MRI and blood biomarkers. Findings: There were no baseline group differences in proteins. Longitudinally, only dual decline showed significant changes in 75 proteins, with PGP9.5 showing the most alteration (p-FDR < 0.05), implicated in synaptic function, proteostasis, and regulation of amyloid precursor protein and amyloid β protein. The top-enriched pathway pointed to mitochondrial protein degradation. Of 75, changes in select proteins were related to future cognitive impairment, brain atrophy patterns, and blood biomarkers of AD, neuroinflammation, and neurodegeneration, with TRI72 being the top significant protein related to cognitive impairment and pTau181 progression. Interpretation: Older adults experiencing dual decline exhibit longitudinal protein changes, indicating mitochondrial dysfunction, proteostasis, neuroinflammation, and immune responses. Funding: None. |
| format | Article |
| id | doaj-art-db003e972a34453d97c3cda9cff8a00a |
| institution | Matheson Library |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-db003e972a34453d97c3cda9cff8a00a2025-08-02T04:47:18ZengElsevierEBioMedicine2352-39642025-08-01118105858Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in contextQu Tian0Erin E. Greig1Michael R. Duggan2Keenan A. Walker3Luigi Ferrucci4Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, 251 Bayview Blvd., Suite 100, Baltimore, MD, USA, 21224; Corresponding author. 251 Bayview Blvd., Suite 100, RM 04B332, Baltimore, MD, 21224, USA.Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, 251 Bayview Blvd., Suite 100, Baltimore, MD, USA, 21224Multimodal Imaging of Neurodegenerative Disease Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, 251 Bayview Blvd., Suite 100, Baltimore, MD, USA, 21224Multimodal Imaging of Neurodegenerative Disease Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, 251 Bayview Blvd., Suite 100, Baltimore, MD, USA, 21224Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, 251 Bayview Blvd., Suite 100, Baltimore, MD, USA, 21224Summary: Background: The simultaneous memory and gait decline is linked to greater dementia risk than memory decline alone. We aim to identify dual decline-related protein changes that may offer valuable insights into biological processes. Methods: We compared longitudinal changes in 7268 plasma proteomic markers in older adults experiencing dual decline, memory decline, and gait decline from no decline (reference) using linear mixed-effects regression and related to brain MRI and blood biomarkers. Findings: There were no baseline group differences in proteins. Longitudinally, only dual decline showed significant changes in 75 proteins, with PGP9.5 showing the most alteration (p-FDR < 0.05), implicated in synaptic function, proteostasis, and regulation of amyloid precursor protein and amyloid β protein. The top-enriched pathway pointed to mitochondrial protein degradation. Of 75, changes in select proteins were related to future cognitive impairment, brain atrophy patterns, and blood biomarkers of AD, neuroinflammation, and neurodegeneration, with TRI72 being the top significant protein related to cognitive impairment and pTau181 progression. Interpretation: Older adults experiencing dual decline exhibit longitudinal protein changes, indicating mitochondrial dysfunction, proteostasis, neuroinflammation, and immune responses. Funding: None.http://www.sciencedirect.com/science/article/pii/S2352396425003020Plasma biomarkerProteomicsCognitionMobilityAgeingDementia |
| spellingShingle | Qu Tian Erin E. Greig Michael R. Duggan Keenan A. Walker Luigi Ferrucci Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context EBioMedicine Plasma biomarker Proteomics Cognition Mobility Ageing Dementia |
| title | Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context |
| title_full | Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context |
| title_fullStr | Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context |
| title_full_unstemmed | Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context |
| title_short | Plasma proteomic signatures of dual cognitive and mobility decline in older adultsResearch in context |
| title_sort | plasma proteomic signatures of dual cognitive and mobility decline in older adultsresearch in context |
| topic | Plasma biomarker Proteomics Cognition Mobility Ageing Dementia |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425003020 |
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