Quantitative phosphoproteomics uncovers dysregulated kinase networks in Alzheimer’s disease

Alzheimer’s disease (AD) is a form of dementia characterized by amyloid-β plaques and Tau neurofibrillary tangles that progressively disrupt neural circuits in the brain. Using mass spectrometry, we performed a combined analysis of the tyrosine, serine, and threonine phosphoproteome, and proteome of post-mortem brain tissue from AD patients and aged matched controls. We used a data-centric approach to identify co-correlated signaling networks associated with cellular and pathological changes. We identified two independent pathology clusters that were associated with Tau and oligodendrocyte pathologies. We observed phosphorylation sites on known Tau-kinases as well as other novel signaling factors that were associated with these clusters. Together, these results build a map of pathology-associated phosphorylation signaling activation events occurring in AD.