title: Age-related appearance of dendritic inclusions in catecholaminergic brainstem neurons.
abstract: We identified p62-immunoreactive inclusions in dendrites of catecholaminergic brainstem projection neurons using antibodies against p62, ubiquitin, α-synuclein, hyperphosphorylated tau, and tyrosine hydroxylase in 100-μm sections through the brainstem dorsal vagal area, locus coeruleus, and substantia nigra of 149 autopsy cases staged for intraneuronal Alzheimer's and Parkinson's disease-associated lesions. The inclusions resembled Marinesco bodies within cell nuclei of catecholaminergic neurons as well as the dot-like structures previously described by Dickson in specific neuropil areas in humans. The p62-positive inclusions were confined to dendrites of catecholaminergic neurons, lacked neuromelanin granules, and were tau- and α-synuclein-negative. Their immunoreactivity for ubiquitin varied and their prevalence significantly increased with advancing age. The presence or absence of Alzheimer's and/or Parkinson's disease-associated pathology did not influence their existence. There was a strong association between the presence of p62-positive inclusions and Marinesco bodies (p < 0.0001). Our results reveal a hitherto unknown alteration within specific neuronal types of the human brainstem that may be independent of the sequestosome-ubiquitin-proteasomal pathway and unrelated to proteinaceous aggregate-formation of neurodegenerative diseases.
authors.affiliation: Clinical Neuroanatomy, Center for Biomedical Research, Department of Neurology, University of Ulm, Ulm, Germany. heiko.braak@uni-ulm.de
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.forename: Jakob
authors.initials: J
authors.lastname: Matschke
authors.forename: Estifanos
authors.initials: E
authors.lastname: Ghebremedhin
authors.forename: Kelly
authors.initials: K
authors.lastname: Del Tredici
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001933:Brain Stem / Q000166:cytology*; D002395:Catecholamines / Q000378:metabolism*; D002648:Child; D003712:Dendrites / Q000502:physiology*; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002395:Catecholamines; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D051844:alpha-Synuclein