Abstract
BMJ Open. 2025 Nov 21;15(11):e107399. doi: 10.1136/bmjopen-2025-107399.
ABSTRACT
INTRODUCTION: Growing evidence points towards the integral role of both central and peripheral inflammation across all neurodegenerative diseases, including dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The immune alterations observed in these diseases may occur long before the onset of clinical and cognitive symptoms; however, the exact timing and role of inflammation in the pathogenesis of neurodegenerative disease remains unclear. Findings to date are conflicting, with most work focused on AD rather than other dementias and most studies from single sites and cross-sectional. Through longitudinally examining detailed phenotypes of the peripheral immune system using mass cytometry, the Immune Profiling in Early Cognitive Disorders study aims to uncover specific immune signatures in early AD and DLB, how these signatures change over time and how they relate to disease progression and cognitive changes.
METHODS AND ANALYSIS: Blood, cerebrospinal fluid, saliva and urine samples will be collected from a cohort of participants with either prodromal (mild cognitive impairment) or early dementia due to Lewy bodies or AD (MCI-LB and DLB; and MCI-AD and AD), alongside healthy controls. Through immunophenotyping with mass cytometry, detailed immune fingerprints will be identified for these groups. We will assess which key combinations of immune cell clusters are predictive of disease phenotype, cognitive decline and progression to dementia. Samples will also be evaluated with novel techniques to measure markers of degenerative pathology and inflammation.
ETHICS AND DISSEMINATION: This study was approved by the Preston North West Research Ethics committee (21/NW/0314) and is registered with the ISRCTN registry (ISRCTN62392656). The study is ongoing (since June 2022). Baseline visits are being undertaken, and follow-up visits have started for some participants. Full data analyses will be completed and submitted for publication upon conclusion of the study.
PMID:41271423 | DOI:10.1136/bmjopen-2025-107399
UK DRI Authors
