Quantitative phosphoproteomics uncovers dysregulated kinase networks in Alzheimer's disease.

Autor: Morshed N; Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Lee MJ; Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Rodriguez FH; Department of Chemical and Materials Engineering, New Mexico State University, Las Cruces, NM, USA., Lauffenburger DA; Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Mastroeni D; Arizona State University-Banner Neurodegenerative Disease Research Center, Tempe, AZ, USA., White FM; Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, USA. fwhite@mit.edu.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. fwhite@mit.edu.; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA. fwhite@mit.edu.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2021 Jun; Vol. 1 (6), pp. 550-565. Date of Electronic Publication: 2021 Jun 14.
DOI: 10.1038/s43587-021-00071-1
Abstrakt: 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. The signaling networks underlying AD pathological changes are poorly characterized at the phosphoproteome level. Using mass spectrometry, we analyzed the proteome and tyrosine, serine and threonine phosphoproteomes of temporal cortex tissue from patients with AD and aged-matched controls. We identified cocorrelated peptide clusters that were linked to varying levels of phospho-tau, oligodendrocyte, astrocyte, microglia and neuron pathologies. We found that neuronal synaptic protein abundances were strongly anti-correlated with markers of microglial reactivity. We also observed that phosphorylation sites on kinases targeting tau and other new signaling factors were correlated with these peptide modules. Finally, we used data-driven statistical modeling to identify individual peptides and peptide clusters that were predictive of AD histopathologies. Together, these results build a map of pathology-associated phosphorylation signaling events occurring in AD.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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