Microglia protein profiles in CSF across Alzheimer's disease clinical stages.
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Blujdea Elena-Raluca, van Bokhoven Pieter, Martino-Adami Pamela V, Marshe Victoria S, Vromen Ellen M, Hok-A-Hin Yanaika S, Boiten Walter A, Irwin David J, Chen-Plotkin Alice S, Lemstra Afina W, Pijnenburg Yolande, van der Flier Wiesje M, Peters Oliver, Hellmann-Regen Julian, Priller Josef, Schneider Anja, Wiltfang Jens, Jessen Frank, Düzel Emrah, Buerger Katharina, Perneczky Robert, Teipel Stefan, Laske Christoph, Brosseron Frederic, DELCODE Consortium, Del Campo Marta, Wijdeven Ruud, Visser Pieter-Jelle, Tijms Betty M, De Jager Philip L, Ramirez Alfredo, Teunissen Charlotte E, Vermunt Lisa
Аннотация
Microglia are implicated in the progression of Alzheimer's disease (AD) pathology from its earliest stages, suggesting that cerebrospinal fluid (CSF) microglia profiling across clinical AD stages can aid in treatment development and monitoring. We analyzed two CSF cohorts (n = 834) that span from unimpaired controls to preclinical and dementia AD stages, identifying 109 dysregulated microglia-related proteins. Enrichment analyses revealed innate immune processes and cellular recruitment in preclinical AD, whereas AD dementia revealed adaptive immunity and macrophage responses. Next, we aligned the in vivo microglia protein profiles with ex vivo-derived microglial transcriptomic signatures, such as disease-associated microglia phenotypes. Transcriptomic signatures were not specific to either clinical stage but spanned both. We classified an 18-protein panel highlighting distinct changes between the preclinical and dementia stages. Our findings underscore the potential of microglia-based biomarker research for AD staging, offering insights into microglia dynamics in clinical AD stages and how transcriptomic signatures translate to proteomic profiles.