Defining Alzheimer’s Disease through Proteomic CSF Profiling

Alzheimer disease (AD) is the main cause of dementia, and its complexity is not yet completely understood. Proteomic profiles can provide useful information to explore the pathways involved and the heterogeneity among AD patients. A proteomic analysis was performed in cerebrospinal fluid (CSF) samples from mild cognitive impairment due to AD (MCI-AD) and control individuals; both groups were classified by amyloid β42/amyloid β40 levels in CSF (data available in BioStudies database (S-BSST1456)). The analysis based on PLS regression and volcano plot identified 7 proteins (FOLR2, PPP3CA, SMOC2, STMN1, TAGLN3, TMEM132B, and UCHL1) mainly related to protein phosphorylation, structure maintenance, inflammation, and protein degradation. Enrichment analysis revealed the involvement of different biological processes related to neuronal mechanisms and synapses, lipid and carbohydrate metabolism, immune system and inflammation, vascular, hormones, and response to stimuli, and cell signaling and adhesion. In addition, the proteomic profile showed some association with the levels of AD biomarkers in CSF. Regarding the subtypes, two MCI-AD subgroups were identified: one could be related to synapsis and neuronal functions and the other to innate immunity. The study of the proteomic profile in the CSF of AD patients reflects the heterogeneity of biochemical pathways involved in AD.