Distinct inflammatory profiles in young‐onset versus late‐onset Alzheimer's disease
Alzheimer's & Dementia, 2025
Thapa S., Anastassiadis C., Vasilevskaya A., Taghdiri F., Jurisica I., Hadian M., Salwierz P., Robbani F., Kivisäkk P., Hyman B., Arnold S., Ingelsson M., Haas W., Lozano A., Tang‐Wai D., Tartaglia M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | CSF |  Olink Explore 3072/384 |
Abstract
INTRODUCTION
Neuroinflammation, a key player in Alzheimer’s disease (AD) pathogenesis, may be differentially involved in young‐onset (YOAD) compared to late‐onset (LOAD) AD.
METHODS
Using proximity extension assay technology, we examined 737 inflammatory markers in the CSF of 26 healthy controls (63.9 ± 8.7; 12♀), 57 patients with YOAD (60.8 ± 4.9 y/o; 40♀), and 33 with LOAD (76.6 ± 4.5 y/o; 18♀). We also assessed biomarkers of AD pathology (Aβ42, p‐tau181, t‐tau) and neurodegeneration (neurofilament light‐chain [NfL]).
RESULTS
Compared to controls, SCRN1 and MMP10 were increased in LOAD and YOAD, but 16 markers showed YOAD‐specific increases. Forty‐six markers were significantly associated with NfL. P‐tau181 and t‐tau mediated the association between inflammatory markers and NfL in YOAD. In LOAD we could not identify a direct or indirect relationship between neuroinflammation and neurodegeneration.
DISCUSSION
Using a proteomics approach, we observed an exacerbation of neuroinflammatory changes and a differential contribution of neuroinflammation to AD pathology and neurodegeneration in YOAD compared to LOAD.
Highlights
Olink’s Proximity Extension Assay was used to compare the inflammatory profile of 26 healthy controls and 90 Alzheimer’s disease (AD) patients.AD patients were further stratified into young‐onset (YOAD, n = 57) and late‐onset (LOAD, n = 33) AD.Cerebrospinal fluid (CSF) levels of MMP10 and SCRN1 were increased in both YOAD and LOAD, but 16 proteins were only increased in YOAD.Tau mediated the association between inflammatory markers and neurodegeneration in YOAD.Neuroinflammation may be differentially involved in the pathogenesis of YOAD compared to LOAD.