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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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Thorn-shaped astrocytes (TSA) are glial fibrillary tangles that contain abnormally phosphorylated and aggregated microtubule-associated tau protein. The present study examines the prevalence of TSA in the human medial temporal lobe of 100 autopsy brains aged 42-97 years (mean age: 65 years). Serial brain sections were cut at 100 microm and stained using phosphorylation-dependent anti-tau antibodies (AT8, PHF-1, TG3, Alz-50) and silver staining methods for neurofibrillary changes and beta-amyloid deposits. TSA preferentially were distributed in periventricular, subependymal, and subpial areas of the mediobasal temporal lobe (MTL). Double-labeling with AT8 and anti-GFAP antibodies demonstrated that the abnormal tau protein was deposited in astroglial cell bodies and in proximal and distal astroglial processes. A pronounced inter-individual variation was noted in the density of AT8-positive TSA, thereby allowing distinction of mild, moderate, and severe involvement. TSA were absent in individuals younger than 60 years. A significant increase in the prevalence of TSA was noted with advancing age. In the age-range of 75-98 years TSA were found in approximately 50% of all individuals. The development of TSA was not correlated with the severity of Alzheimer-related cortical pathology. In summary, this study suggests that TSA is a distinct form of glial tau pathology that occurs with a high frequency in elderly individuals.

Sporadic Parkinson's disease involves multiple neuronal systems and results from changes developing in a few susceptible types of nerve cells. Essential for neuropathological diagnosis are alpha-synuclein-immunopositive Lewy neurites and Lewy bodies. The pathological process targets specific induction sites: lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays and cortical areas gradually become affected. The disease process in the brain stem pursues an ascending course with little interindividual variation. The pathology in the anterior olfactory nucleus makes fewer incursions into related areas than that developing in the brain stem. Cortical involvement ensues, beginning with the anteromedial temporal mesocortex. From there, the neocortex succumbs, commencing with high order sensory association and prefrontal areas. First order sensory association/premotor areas and primary sensory/motor fields then follow suit. This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.