Defining Alzheimer's Disease through Proteomic CSF Profiling

Area of Science:

• Neuroscience
• Biochemistry
• Proteomics

Background:

• Alzheimer disease (AD) is a leading cause of dementia with incompletely understood complexity.
• Proteomic profiling offers insights into AD pathways and patient heterogeneity.

Purpose of the Study:

• To investigate proteomic profiles in cerebrospinal fluid (CSF) from individuals with mild cognitive impairment due to AD (MCI-AD) and controls.
• To identify proteins and biological processes associated with MCI-AD and AD biomarkers.

Main Methods:

• Proteomic analysis of CSF samples from MCI-AD and control groups.
• Classification of participants based on CSF amyloid β42/amyloid β40 levels.
• Analysis using Partial Least Squares (PLS) regression and volcano plots.

Main Results:

• Identified 7 key proteins (FOLR2, PPP3CA, SMOC2, STMN1, TAGLN3, TMEM132B, UCHL1) linked to phosphorylation, structure, inflammation, and degradation.
• Enrichment analysis indicated involvement of neuronal, synaptic, metabolic, immune, vascular, and signaling pathways.
• Discovered two MCI-AD subgroups: one associated with synaptic/neuronal functions, the other with innate immunity.
• Proteomic profiles showed associations with CSF AD biomarker levels.

Conclusions:

• CSF proteomic profiles reflect the biochemical heterogeneity of Alzheimer disease.
• Distinct MCI-AD subgroups suggest different underlying pathological mechanisms, potentially impacting therapeutic strategies.