Alzheimer's blood test could track disease progression earlier and more precisely
Researchers identified 18 brain proteins in spinal fluid that distinguish early-stage Alzheimer's from advanced dementia, potentially enabling doctors to monitor disease progression and test new treatments more effectively. The finding transforms microglia—immune cells implicated in Alzheimer's—from research curiosities into practical diagnostic tools that could reshape clinical trials and patient management.
Originaltitel: Microglia protein profiles in CSF across Alzheimer’s disease clinical stages
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.