Journal of Neuropathology and Experimental Neurology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Subcellular Changes in Bridging Integrator 1 Protein Expression in the Cerebral Cortex During the Progression of Alzheimer Disease Pathology
Genome-wide association studies have established BIN1 (Bridging Integrator 1) as the most significant late-onset Alzheimer disease (AD) susceptibility locus after APOE. We analyzed BIN1 protein expression using automated immunohistochemistry on the hippocampal CA1 region in 19 patients with either no, mild, or moderate-to-marked AD pathology, who had been assessed by Clinical Dementia Rating and CERAD scores. We also examined the amygdala, prefrontal, temporal, and occipital regions in a subset of these patients. In non-demented controls without AD pathology, BIN1 protein was expressed in white matter, glia, particularly o...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Adams, S. L., Tilton, K., Kozubek, J. A., Seshadri, S., Delalle, I. Tags: Original Articles Source Type: research

The Effect of the APOE4 Gene on Accumulation of A{beta}40 After Brain Injury Cannot Be Reversed by Increasing apoE4 Protein
We report a biphasic response of soluble apoE protein after TBI with an acute reduction at 1 day postinjury followed by an increase at 7 days postinjury. TBI-induced Aβ40 levels decreased as soluble apoE levels increased. In APOE4 mice there was a diminished apoE response to TBI that corresponded to prolonged accumulation of TBI-induced Aβ40 versus that in APOE3 mice. Amyloid precursor protein processing was similar in APOE3 and APOE4 mice suggesting that impaired clearance was responsible for the abnormal accumulation of Aβ40 in the latter. Treatment of APOE4 mice with bexarotene for 7 days increased apoE4 ...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Washington, P. M., Burns, M. P. Tags: Original Articles Source Type: research

Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease
Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt–Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the res...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Ansoleaga, B., Garcia-Esparcia, P., Llorens, F., Hernandez-Ortega, K., Carmona, M., Antonio del Rio, J., Zerr, I., Ferrer, I. Tags: Original Articles Source Type: research

Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition
Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Filon, J. R., Intorcia, A. J., Sue, L. I., Vazquez Arreola, E., Wilson, J., Davis, K. J., Sabbagh, M. N., Belden, C. M., Caselli, R. J., Adler, C. H., Woodruff, B. K., Rapscak, S. Z., Ahern, G. L., Burke, A. D., Jacobson, S., Shill, H. A., Driver-Dunckley Tags: Original Articles Source Type: research

Delayed Hypoxemia Following Traumatic Brain Injury Exacerbates White Matter Injury
Hypoxemia immediately following traumatic brain injury (TBI) has been observed to exacerbate injury. However, it remains unclear whether delayed hypoxemia beyond the immediate postinjury period influences white matter injury. In a retrospective clinical cohort of children aged 4–16 years admitted with severe TBI, 28/74 (35%) patients were found to experience delayed normocarbic hypoxemia within 7 days of admission. Based on these clinical findings, we developed a clinically relevant mouse model of TBI with delayed hypoxemia by exposing 5-week old (adolescent) mice to hypoxic conditions for 30 minutes starting 24 hour...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Parikh, U., Williams, M., Jacobs, A., Pineda, J. A., Brody, D. L., Friess, S. H. Tags: Original Articles Source Type: research

Expression of TRPC6 and BDNF in Cortical Lesions From Patients With Focal Cortical Dysplasia
Focal cortical dysplasia (FCD) likely results from abnormal migration of neural progenitor cells originating from the subventricular zone. To elucidate the roles in molecules that are involved in neural migration pathway abnormalities in FCDs, we investigated the expression patterns of transient receptor potential canonical channel 6 (TRPC6) and brain-derived neurotrophic factor (BDNF) in cortical lesions from FCD patients and in samples of normal control cortex. TRPC6 and BDNF mRNA and protein levels were increased in FCD lesions. By immunohistochemistry, they were strongly expressed in microcolumns, heterotopic neurons, ...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Zheng, D.-H., Guo, W., Sun, F.-J., Xu, G.-Z., Zang, Z.-L., Shu, H.-F., Yang, H. Tags: Original Articles Source Type: research

JC Virus Infects Neurons and Glial Cells in the Hippocampus
The human polyomavirus JC (JCV) infects glial cells and is the etiologic agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy. JCV can infect granule cell neurons of the cerebellum, causing JCV granule cell neuronopathy and cortical pyramidal neurons in JCV encephalopathy. Whether JCV also infects neurons in other areas of the CNS is unclear. We determined the prevalence and pattern of JCV infection of the hippocampus in archival samples from 28 patients with known JCV infection of the CNS and 66 control subjects. Among 28 patients, 11 (39.3%) had JCV infection of hippocampus structures demonst...
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Authors: Wüthrich, C., Batson, S., Anderson, M. P., White, L. R., Koralnik, I. J. Tags: Original Articles Source Type: research

In This Issue
(Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - July 10, 2016 Category: Neurology Tags: In This Issue Source Type: research

Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans
Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas ...
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Dickinson, P. J., York, D., Higgins, R. J., LeCouteur, R. A., Joshi, N., Bannasch, D. Tags: Original Articles Source Type: research

Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture
Saccular intracranial aneurysm (sIA) aneurysm causes intracranial hemorrhages that are associated with high mortality. Lipid accumulation and chronic inflammation occur in the sIA wall. A major mechanism for lipid clearance from arteries is adenosine triphosphate-binding cassette A1 (ABCA1)-mediated lipid efflux from foam cells to apolipoprotein A-I (apoA-I). We investigated the association of wall degeneration, inflammation, and lipid-related parameters in tissue samples of 16 unruptured and 20 ruptured sIAs using histology and immunohistochemistry. Intracellular lipid accumulation was associated with wall remodeling (p =...
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Ollikainen, E., Tulamo, R., Lehti, S., Lee-Rueckert, M., Hernesniemi, J., Niemelä, M., Ylä-Herttuala, S., Kovanen, P. T., Frösen, J. Tags: Original Articles Source Type: research

Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia
We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-...
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Garbuzova-Davis, S., Haller, E., Tajiri, N., Thomson, A., Barretta, J., Williams, S. N., Haim, E. D., Qin, H., Frisina-Deyo, A., Abraham, J. V., Sanberg, P. R., Van Loveren, H., Borlongan, C. V. Tags: Original Articles Source Type: research

Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum
In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10. To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, ...
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Barca, E., Kleiner, G., Tang, G., Ziosi, M., Tadesse, S., Masliah, E., Louis, E. D., Faust, P., Kang, U. J., Torres, J., Cortes, E. P., Vonsattel, J.-P. G., Kuo, S.-H., Quinzii, C. M. Tags: Original Articles Source Type: research

Blood-Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy
This report represents the first description of BBB dysfunction in a pathologically proven CTE case and suggests a vascular component in the postconcussion cascade of events that may ultimately lead to development of a progressive degenerative disorder. BBB dysfunction may represent a correlate of neural dysfunction in live subjects suspected of being at risk for development of CTE. (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Doherty, C. P., OKeefe, E., Wallace, E., Loftus, T., Keaney, J., Kealy, J., Humphries, M. M., Molloy, M. G., Meaney, J. F., Farrell, M., Campbell, M. Tags: Original Articles Source Type: research

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers
Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological asses...
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Ojo, J. O., Mouzon, B., Algamal, M., Leary, P., Lynch, C., Abdullah, L., Evans, J., Mullan, M., Bachmeier, C., Stewart, W., Crawford, F. Tags: Original Articles Source Type: research

Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study
We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects ≥50 years of age from São Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 ± 9.4 years); it rarely occurred as an isolated neuropatho...
Source: Journal of Neuropathology and Experimental Neurology - June 15, 2016 Category: Neurology Authors: Rodriguez, R. D., Suemoto, C. K., Molina, M., Nascimento, C. F., Leite, R. E. P., de Lucena Ferretti-Rebustini, R. E., Farfel, J. M., Heinsen, H., Nitrini, R., Ueda, K., Pasqualucci, C. A., Jacob-Filho, W., Yaffe, K., Grinberg, L. T. Tags: Original Articles Source Type: research