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Theoretical Impact of Florbetapir (18F) Amyloid Imaging on Diagnosis of Alzheimer Dementia and Detection of Preclinical Cortical Amyloid
AbstractIn 2012, florbetapir (18F) (Amyvid) received US Food and Drug Administration approval as a diagnostic agent for detecting neuritic (β-amyloid) plaques in living patients. Although such approval is specifically not extended to the use of florbetapir as a single definitive diagnostic test for Alzheimer disease dementia (ADD), it is of considerable importance to examine its potential in this regard. To estimate the ability of florbetapir amyloid imaging to detect specified densities of postmortem-identified neuritic plaques, we used the data of Clark et al [Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with ...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research

Regional Neurodegeneration and Gliosis Are Amplified by Mild Traumatic Brain Injury Repeated at 24-Hour Intervals
AbstractMost traumatic brain injuries (TBIs) that occur every year are classified as “mild.” Individuals involved in high-risk activities may sustain multiple mild TBIs. We evaluated the acute physiologic and histopathologic consequences of mild TBI in a mouse model, comparing sham injury, single impact, or 5 impacts at a 24- or 48-hour interinjury interval. A single closed skull impact resulted in bilateral gliosis in the hippocampus and entorhinal cortex that was proportional to impact depth. Midline impact, at a depth just above the threshold to induce transient unconsciousness, produced occasional axonal injury and...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research

Histopathologic Features of Intracranial Vascular Involvement in Fibromuscular Dysplasia, Ehlers-Danlos Type IV, and Neurofibromatosis I
AbstractNonatherosclerotic cerebrovascular arteriopathies share epidemiologic and clinical features, but few studies directly compare histologic features of the intracranial vasculature. We studied 3 adult autopsy cases of fibromuscular dysplasia in patients who died of basilar artery aneurysm rupture, vertebral artery dissection, or Moyamoya syndrome. Fibromuscular dysplasia was only identified when multiple sections (optimally of the entire circle of Willis) were examined by microscopy. A fourth case of a massive subcutaneous scalp cirsoid aneurysm with classic “string-of-beads” gross appearance and microscopic media...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research

Alterations of the RRAS and ERCC1 Genes at 19q13 in Gemistocytic Astrocytomas
AbstractGemistocytic astrocytoma (World Health Organization grade II) is a rare variant of diffuse astrocytoma that is characterized by the presence of neoplastic gemistocytes and has a significantly less favorable prognosis. Other than frequent TP53 mutations (>80%), little is known about its molecular profile. Here, we show that gemistocytic astrocytomas carry a lower frequency of IDH mutations than fibrillary astrocytomas (74% vs 92%; p = 0.0255) but have profiles similar to those of fibrillary astrocytomas with respect to TERT promoter mutations (5% vs 0%), 1p/19q loss (10% vs 8%), and loss of heterozygosity 10q (10% v...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research

In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: In This Issue Source Type: research

Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Expression Is an Independent Prognostic Factor in Pediatric Pilocytic and Pilomyxoid Astrocytoma
This study aimed to determine the expression and prognostic value of IMP3 in pediatric PA/PMAs. Insulin-like growth factor 2 mRNA binding protein 3 protein expression was examined by immunohistochemistry in 77 pediatric PAs (n = 70) and PMAs (n = 7) and scored on a subjective scale. Strong diffuse staining for IMP3 was observed in 31% (24 of 77) of tumors and associated with a shorter progression-free survival (hazard ratio, 2.63; p = 0.008). This cohort confirmed previously identified prognostic factors, including extent of resection, age, and tumor location. Currently, only clinical factors are weighed to stratify risk f...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Original Articles Source Type: research

A “Weighted” Fluorescence In Situ Hybridization Strengthens the Favorable Prognostic Value of 1p/19q Codeletion in Pure and Mixed Oligodendroglial Tumors
Abstract: Evaluation of the molecular status of 1p and 19q is a major relevant diagnostic, prognostic, and predictive tool for oligodendroglial brain tumors. Fluorescence in situ hybridization (FISH) is the most commonly used technique for determining 1p and 19q allelic losses, but it lacks fully standardized criteria for analysis. This lack of standardization has led to interinstitutional disagreement in the interpretation of results, thereby contributing to a “gray prognostic zone” that includes codeleted patients with an unexpectedly unfavorable outcome. To optimize the prognostic potential of 1p/19q status determin...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Original Articles Source Type: research

Brain Microvascular Accumulation and Distribution of the NOTCH3 Ectodomain and Granular Osmiophilic Material in CADASIL
Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial brain arteriopathy, is associated with deposition of granular osmiophilic material (GOM). We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls. We observed intense immunostaining patterns with ...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Original Articles Source Type: research

Chemically Induced Rat Schwann Cell Neoplasia as a Model for Early-Stage Human Peripheral Nerve Sheath Tumors: Phenotypic Characteristics and Dysregulated Gene Expression
Abstract: Most malignant human tumors display a high degree of intratumoral heterogeneity at the time of diagnosis that contributes to treatment failure. This also applies to malignant peripheral nerve sheath tumors (MPNSTs) and aggressive soft tissue sarcomas that arise sporadically or in the context of neurofibromatosis type 1. On average, MPNSTs measure 10 cm in diameter at diagnosis. To explore molecular changes associated with early malignant progression and that may be present in most, if not all, tumor cells, we generated expression profiles of ethylnitrosourea-induced trigeminal MPNSTs in rats. Because these tumors...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Original Articles Source Type: research

Human Apolipoprotein E4 Worsens Acute Axonal Pathology but Not Amyloid-β Immunoreactivity After Traumatic Brain Injury in 3xTG-AD Mice
Abstract: Apolipoprotein E4 (APOE4) genotype is a risk factor for poor outcome after traumatic brain injury (TBI), particularly in young patients, but the underlying mechanisms are not known. By analogy to effects of APOE4 on the risk of Alzheimer disease (AD), the APOE genotype may influence β-amyloid (Aβ) and tau deposition after TBI. To test this hypothesis, we crossed 3xTG-AD transgenic mice carrying 3 human familial AD mutations (PS1M146V, tauP301L, and APPSWE) to human ApoE2-, ApoE3-, and ApoE4-targeted replacement mice. Six- to 8-month-old 3xTG-ApoE mice were assayed by quantitative immunohistochemistry for amyloi...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Original Articles Source Type: research

Synaptic Changes in the Dentate Gyrus of APP/PS1 Transgenic Mice Revealed by Electron Microscopy
Abstract: Numerous studies have reported widespread synaptic dysfunction or loss in early stages of both Alzheimer disease (AD) patients and animal models; it is widely accepted that synapse loss is the major structural correlate of cognitive dysfunction. Elucidation of the changes that may affect synapses is crucial for understanding the pathogenic mechanisms underlying AD, but ultrastructural preservation of human postmortem brain tissue is often poor, and classical methods for quantification of synapses have significant technical limitations. We previously observed changes in dendritic spines in plaque-free regions of t...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Original Articles Source Type: research

How Does the Brain Limit the Severity of Inflammation and Tissue Injury During Bacterial Meningitis?
Abstract: The most devastating CNS bacterial infection, bacterial meningitis, has both acute and long-term neurologic consequences. The CNS defends itself against bacterial invasion through a combination of physical barriers (i.e. blood-brain barrier, meninges, and ependyma), which contain macrophages that express a range of pattern-recognition receptors that detect pathogens before they gain access to the CNS and cerebrospinal fluid. This activates an antipathogen response consisting of inflammatory cytokines, complement, and chemoattractants. Regulation of the antipathogen inflammatory response is essential for preventin...
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: Review Article Source Type: research

In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - May 1, 2013 Category: Neurology Tags: In this Issue Source Type: research