The Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases

2017/11/22 by Peter T. Nelson, Peter T Nelson, Erin L Abner +21 · 154 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Alzheimer's disease research and treatments #Amygdala #Biology #Central nervous system #Disease #Gene #Genetics #Locus (genetics) #Locus coeruleus #Medicine #Neurological diseases and metabolism #Neuroscience #Parkinson's disease #Pathology #Prion Diseases and Protein Misfolding

paper · pdf · doi:10.1093/jnen/nlx099

published in Journal of Neuropathology & Experimental Neurology 77(1), 2-20 (Oxford University Press)

openalex publication_date 2017/11/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

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 age-related 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.

Citations

• Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction
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