Relation of different CSF biosignatures to clinical phenotypes in a memory clinic cohort

Abstract Background The heterogeneity of a multifactorial disease like Alzheimer’s disease (AD) cannot be captured solely with ATN biomarkers. Previous research has identified mixed neuropathologies as well as subtypes discovered by brain scans and cerebrospinal fluid (CSF) proteomics in AD cohorts. Still, we need a better understanding of how clinical characteristics distribute between subgroups of AD. Additionally, various approaches determining subgroups need to be evaluated. AD, which falls under the umbrella term dementia, could in fact also be considered an umbrella itself with distinct subgroups. Method Altogether 288 CSF samples from patients from the Karolinska University Hospital memory clinic in Solna, Sweden, were analysed. Patients in the cohort were diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and different dementias, mainly AD. Using an antibody‐based suspension bead array, levels of 75 proteins were measured. Clustering analysis methods were used to identify subgroups. Result The assessed panel reveals differences in patterns of protein levels within diagnostic groups and by applying clustering analyses subgroups across the dementia spectrum can be identified. Furthermore, Gene Ontology search implies differences in plausible underlying disease mechanisms between the distinct subgroups. It is of interest to explore to what extent, e.g., cardiovascular conditions or psychological burden are represented in the subgroups. Conclusion Identifying subgroups within different diagnostic groups may prove to be crucial for finding the most suitable prevention and treatment options, particularly when disease modifying drugs are developed and tested.