Plasma neuroimmune pathway signatures are associated with clinical impairment and lower MRI-derived hippocampal volume across the Alzheimer's disease continuum.

Mubarak Alruwaili, Muhannad Faleh Alanazi, Hailah M Almohaimeed, Saud S Alharbi, Nourah Alruwais, Eman Ali Elkordy, Mohammed S Alshuhri

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Article in European geriatric medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Mubarak AlruwailiDepartment of Internal Medicine, College of Medicine, Jouf University, Sakaka, Saudi Arabia.

Muhannad Faleh AlanaziDepartment of Internal Medicine, Division of Radiology, College of Medicine, Jouf University, Sakaka, Saudi Arabia.

Hailah M AlmohaimeedDepartment of Basic Science, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, 11671, Riyadh, Saudi Arabia.

Saud S AlharbiAssistant Professor Family Medicine, Consultant Family Medicine, Department of Family and Community Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. Salrehily@ut.edu.sa.ORCID http://orcid.org/0009-0009-0563-839X

Nourah AlruwaisHealth Science Department, College of Applied Studies, King Saud University, Riyadh, Saudi Arabia.

Eman Ali ElkordyAnatomy and Physiology Department, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.

Mohammed S AlshuhriRadiology and Medical Imaging Department, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia.

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6 · The paper itself

Abstract

methodsThis retrospective observational study included 506 Alzheimer's Disease Neuroimaging Initiative participants: 53 cognitively normal individuals, 352 with mild cognitive impairment, and 101 with dementia. Plasma proteins from the quality-controlled Rules-Based Medicine multiplex dataset were standardized and grouped into five circulating protein scores: complement-acute-phase, endothelial-associated, extracellular matrix remodeling, myeloid, and interleukin. Outcomes included Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, Functional Activities Questionnaire, normalized hippocampal volume, and normalized brain volume. Multivariable models were adjusted for age, sex, education, and APOE ε4 carrier status.

resultsIn the primary cross-sectional pathway-level analyses, complement-acute-phase scores were higher in participants with dementia than in cognitively normal participants after FDR correction (β = 0.314, 95% CI 0.118 to 0.511; FDR q = 0.018). Higher complement-acute-phase scores were associated with lower MMSE (β = -0.859; FDR q < 0.001), higher CDR-SB (β = 0.622; FDR q < 0.001), and higher FAQ scores (β = 2.473; FDR q < 0.001). Higher endothelial-associated plasma protein scores were associated with lower normalized hippocampal volume (β = -1.47 × 10⁻

conclusionsPlasma neuroimmune signatures showed pathway-specific associations with Alzheimer's disease-related phenotypes, with complement-acute-phase score linked most consistently to clinical impairment and endothelial-associated circulating protein profile linked to hippocampal volume.

Indexed as

Alzheimer’s diseaseCognitive impairmentComplement pathwayHippocampal volumeInnate immunityNeuroinflammationPlasma biomarkers

Identifiers

PMID42711543

DOI10.1038/s43587-021-00073-z

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