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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.
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
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
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
see page 260