The amygdala as a locus of pathologic misfolding in neurodegenerative diseases

Peter T. Nelson, Erin L. Abner, Ela Patel, Sonya Anderson, Donna M. Wilcock, Richard J. Kryscio, Linda J. Van Eldik, Gregory A. Jicha, Zsombor Gal, Ruth S. Nelson, Bela G. Nelson, Jozsef Gal, Md Tofial Azam, David W. Fardo, Matthew D. Cykowski

Research output: Contribution to journalReview articlepeer-review

77 Scopus citations


Over the course of most common neurodegenerative diseases the amygdala accumulates pathologically misfolded proteins. Misfolding of 1 protein in aged brains often is accompanied by the misfolding of other proteins, suggesting synergistic mechanisms. The multiplicity of pathogenic processes in human amygdalae has potentially important implications for the pathogenesis of Alzheimer disease, Lewy body diseases, chronic traumatic encephalopathy, primary agerelated tauopathy, and hippocampal sclerosis, and for the biomarkers used to diagnose those diseases. Converging data indicate that the amygdala may represent a preferential locus for a pivotal transition from a relatively benign clinical condition to a more aggressive disease wherein multiple protein species are misfolded. Thus, understanding of amygdalar pathobiology may yield insights relevant to diagnoses and therapies; it is, however, a complex and imperfectly defined brain region. Here, we review aspects of amygdalar anatomy, connectivity, vasculature, and pathologic involvement in neurodegenerative diseases with supporting data from the University of Kentucky Alzheimer's Disease Center autopsy cohort. Immunohistochemical staining of amygdalae for Aβ, Tau, α-synuclein, and TDP-43 highlight the often-coexisting pathologies. We suggest that the amygdala may represent an "incubator" for misfolded proteins and that it is possible that misfolded amygdalar protein species are yet to be discovered.

Original languageEnglish (US)
Pages (from-to)2-20
Number of pages19
JournalJournal of Neuropathology and Experimental Neurology
Issue number1
StatePublished - Jan 1 2018


  • Amyloid
  • Entorhinal
  • Hippocampus
  • Neuropathology
  • Proteomics
  • SNAP
  • Subpial
  • tau Proteins/metabolism
  • Humans
  • Neurodegenerative Diseases/metabolism
  • DNA-Binding Proteins/metabolism
  • Protein Folding
  • Amygdala/metabolism
  • Amyloid beta-Peptides/metabolism
  • alpha-Synuclein/metabolism

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience
  • Pathology and Forensic Medicine


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