In This Issue

Journal of Neuropathology & Experimental Neurology, Mar 2018

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In This Issue

The Ins Cells 0 1 Pediatric Chordomas: A New Perspective 0 1 0 Conformation-Dependent Anti-Tau Monoclonal Antibodies , mAbs 1 b-Actin Cleavage Following Focal Ischemia CNS Dendritic Selected Autophagy in Feline NiemannPick Disease Type C1 (NPC1) Tau Oligomers Appear Early in Vulnerable Subgroups of the Nucleus Basalis in the March to Alzheimer Disease VC 2018 American Association of Neuropathologists, Inc. All rights reserved. - and De Laere et al describe the roles and migratory pathways of DC in human inflammatory CNS diseases, particularly multiple sclerosis, and corresponding animal models. They highlight gaps in current understanding of these processes and summarize how current MS therapies may affect DC migration patterns. see page 178 Zika Virus in the Postnatal Brain It is well established that immature (1st and 2nd trimester) brains are susceptible to Zika virus infection resulting in microcephaly and related pathologies. An ongoing question is whether the virus can persist and continue to induce brain injury. Chimelli et al report on a child who lived 5 months postnatally after a documented first trimester Zika infection. There was ongoing brain injury and evidence of persistent, though difficult to identify, infection. see page 193 CSF1R-mediated signaling is constitutive in microglia and promotes cell survival, proliferation, and differentiation. Knight et al examine CSF1R signaling in the SIV/macaque model of HIV infection. Their results show coordinate upregulation of both CSF1R and its ligand, CSF1, and implicate this signaling pathway in progressive HIV CNS disease. see page 199 A multicentric retrospective study of pediatric chordomas examined clinical data along with treatment modalities and outcome. A histopathological/immunohistochemical grading system recently crafted for adults was also applied. The authors describe the results of these correlative studies. see page 207 Gibbons et al report the generation, characterization and immunohistochemical application of 2 anti-tau mAbs that distinguish Alzheimer disease (AD)/aging-related tau pathology from that of other tauopathies, including corticobasal degenerations, progressive supranuclear palsy and Pick disease. These mAbs have the potential to be very useful reagents for dementia research and for clinical diagnosis, particularly for distinguishing cases with mixed tau pathologies. see page 216 LC3 accumulated in axonal balloonings of climbing fibers arising from subdivisions of the inferior olive in cats suffering from NPC1 decreases following intrathecal 2-hydroxypropyl-beta cyclodextrin administration, thus suggesting altered autophagy in certain cerebellar pathways and its amelioration with cyclodextrin. see page 229 Tiernan et al used immunohistochemistry to study the distribution of tau oligomers within cholinergic basal forebrain (CBF) neurons in autopsy brains from 33 subjects across the clinical continuum including normal cognition, mild cognitive impairment, and mild AD. They found that tau oligomers were present in CBF neurons early in the disease and that their accumulation mirrored the previously described caudal to rostral progression of cell loss within CBF neuronal subgroups. They conclude that tau oligomer formation is an early event in the disease course that contributes to known patterns of selective vulnerability within the CBF. see page 246 With the long-term goal of identifying neuroprotective molecules that could be exploited therapeutically, Ye et al demonstrate a connection between actin cleavage and DNA fragmentation in the middle cerebral artery occlusion model in rats. A striking finding in this study is the inhibition of granzyme-mediated DNA fragmentation by intact actin in vitro. see page 260


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In This Issue, Journal of Neuropathology & Experimental Neurology, 2018, 177, DOI: 10.1093/jnen/nly005