Journal of Neuropathology & Experimental Neurology:
In This Issue
Breaking it Down
Traumatic brain injury (TBI) commonly results in traumatic axonal injury in white matter tracts, a poorly understood process that has variable long-term effects. Sullivan et al carefully defined the axonal and glial responses during the first week of this process and delineated a series of complex and diverse glial responses to traumatic axonal injury. This information has important implications for both the treatment and neuroimaging of TBI patients.
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Decreased Hypothalamic Prohormone Convertase (PC) Expression in Huntington Disease (HD)
Hypothalamic neuropeptidergic systems are unequally affected at the peptide and mRNA levels in HD. van Wamelen et al postulated that there might be posttranscriptional or posttranslational processing underlying this and assessed PC expression in hypothalamic and cortical regions in HD patients and controls. In HD patients, PC1/3 and PC2 expression was decreased in infundibular and paraventricular nuclei. Their data suggest that defects in the processing of hypothalamic neuropeptides in HD may partially arise from region-specific decreased PC expression underlying various clinical manifestations in HD.
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pSTAT3 and Inflammation in MS – Active or Reactive?
Activation of STAT3 by phosphorylation increases markedly after CNS insults. In this study, Lu et al show that pSTAT3 does not correlate with inflammatory activity in MS lesions. It was, however, significantly greater in white matter adjacent to active vs. inactive lesions. Their findings support a role for pSTAT3 in regulating reactive changes proximal to MS lesions.
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Neurofibrillary Tau: Is the First Cut the Deepest?
Jarero-Basulto et al found that although non-fibrillary aggregates of Asp421-truncated tau in Alzheimer disease (AD) brains did not increase with respect to Braak staging, Asp421-truncation can be produced by caspase-3 in vitro and in situ in NFTs in AD brain slices. They suggest that generation of early aggregates of the caspase-3-generated pathological Asp421-truncation of tau in long-lasting fibrillary structures may propagate neurodegeneration in the brains of AD patients.
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Looking Into the Pedunculopontine Nucleus in Lewy Body Disease
Hepp et al found different patterns of neuronal loss and Parkinson and Alzheimer disease pathology in the pedunculopontine nucleus pars compacta in Parkinson disease and dementia with Lewy body disease even though all subjects had visual hallucinations. Their results suggest that there may be more general differences in cholinergic degeneration in these two disorders.
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Bad Actors Drink From Leaky Vessels Hastily Decorated With Disorganized Murals
Both glioblastomas (GBM) and pilocytic astrocytomas (PA) exhibit vascular proliferation, albeit of a different nature. Mustafa et al studied proliferating vessels in these 2 tumor types by microscopy and cDNA microarray. Proliferating vessels in PA retain many morphologic characteristics of normal vessels, while those of GBM contain disorganized vascular walls. GBM showed greater upregulation of angiogenic pathway mRNAs compared to PA. The hepatic fibrosis/hepatic stellate cell activation pathway was prominently upregulated in both tumor types.
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Senile Plaques Resurrected as a Correlate of Cognitive Impairment
The authors evaluated clinical and neuropathologic data from the NACC dataset for 835 subjects autopsied from 2005-2012. They found that neurofibrillary tangles and neuritic senile plaques both independently predicted lower cognitive function but, in addition, severe small vessel disease, severe cerebral amyloid angiopathy, and hippocampal sclerosis showed positive correlations with cognitive impairment, indicating that many neuropathologic substrates contribute to loss of cognitive function. Mild to moderate dementia remained unexplained in 14% of patients.
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What’s That Smell? Thiamine Deficiency Induces Olfactory Damage
Wernicke-Korsakoff syndrome (WKS) results from severe acute deficiency of thiamine (vitamin B1) in the setting of chronic alcoholism. Hamada et al discovered massive olfactory bulb interneuronal cell death in a rodent model of WKS, which could be suppressed by an NMDA antagonist. The findings should stimulate neurologists and neuropathologists to examine the olfactory system of WKS patients and suggest approaches to acute therapeutic intervention.
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Confluence of α-Synuclein, Tau and β-Amyloid Pathologies in Dementia With Lewy Bodies (DLB)
Colom-Cadena et al report that the severity of β-amyloid deposition and MAPT H1 haplotype, but not tau deposition, correlate with α-synuclein deposits in DLB, and that hyperphosphorylated tau and α-synuclein co-localize in a subset of Lewy bodies and neurites mainly in the entorhinal cortex and amygdala. These findings show convergence of contributing factors, namely β-amyloid, MAPT haplotype and α-synuclein, in DLB, and reveal specific vulnerability of selected neuronal groups to combined deposition of altered tau and α-synuclein.
see page 1203
© 2013 by American Association of Neuropathologists, Inc.