Abstract:
:We review the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic criteria of s-IBM. We discuss the possible pathogenic role of several themes, such as 1) increased amyloid-beta precursor protein (AbetaPP) and of its fragment Abeta; 2) phosphorylation of tau protein; 3) oxidative stress; 4) abnormal a) signal-transduction, b) transcription, and c) RNA accumulation; 5) "junctionalization" and myogenous" denervation; and 6) lymphocytic inflammation. Evidence is provided supporting our hypothesis that overexpression of AbetaPP within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease (AD) brain are discussed, and the possible cause and significance are addressed.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Askanas V,Engel WKdoi
10.1093/jnen/60.1.1subject
Has Abstractpub_date
2001-01-01 00:00:00pages
1-14issue
1eissn
0022-3069issn
1554-6578journal_volume
60pub_type
杂志文章,评审abstract::Reactive axonal change has long been recognized as a feature of traumatic brain injury. To date, the histological methods used to identify reactive axons have been of limited utility, and they have not provided insight into the initial intraaxonal event that triggers reactive change. In this investigation, monoclonal ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199203000-00006
更新日期:1992-03-01 00:00:00
abstract::Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for ia...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318182f36e
更新日期:2008-09-01 00:00:00
abstract::Werdnig-Hoffmann disease (WHD) is the most severe clinical type of spinal muscular atrophy characterized by loss of lower motor neurons and paralysis. We examined the hypothesis that disease pathogenesis is based on an inappropriate persistence of normally occurring motor neuron programmed cell death. The diagnosis of...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.5.398
更新日期:2000-05-01 00:00:00
abstract::Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e318040ad5c
更新日期:2007-04-01 00:00:00
abstract::This study determined if hippocampal AMPA and NMDA subunit immunoreactivity (IR) in temporal lobe epilepsy patients was increased compared with nonseizure autopsies. Hippocampi from hippocampal sclerosis patients (HS; n = 26) and nonsclerosis cases (non-HS: n = 12) were compared with autopsies (n = 6) and studied for ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199806000-00008
更新日期:1998-06-01 00:00:00
abstract::The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the exp...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000182982.09978.66
更新日期:2005-10-01 00:00:00
abstract::The sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant mortality in the United States today, with an overall rate of 0.39/1000 live births. It is defined as the sudden and unexpected death of an infant <12 months of age that remains unexplained after a complete autopsy, death scene investi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/nlz062
更新日期:2019-09-01 00:00:00
abstract::Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut e...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.1.75
更新日期:2003-01-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199305000-00008
更新日期:1993-05-01 00:00:00
abstract::This report describes a phenotypic differentiation pattern conceived to distinguish invading monocytes from resident microglia in frozen and formalin-fixed human CNS. Phagocytic cells in normal and diseased CNS (multiple sclerosis and encephalitis) were studied immunohistochemically with a panel of antibodies, and phe...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199409000-00008
更新日期:1994-09-01 00:00:00
abstract::LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated cha...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000228205.19915.20
更新日期:2006-09-01 00:00:00
abstract::Intracranial hemangiopericytic meningiomas (HM) from seven patients were examined by immunostaining, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and cell culture. Positive staining for Factor VIII-related antigen was restricted to capillary endothelial cells. There was no reaction with a...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198701000-00006
更新日期:1987-01-01 00:00:00
abstract::Increasing evidence has demonstrated a vital role of microRNAs (miRNAs) in diverse biological processes. However, their functions in developing brain with hypoxia-ischemia (HI) remain largely unknown. Through a miRNA microarray analysis in a P10 rat model of cerebral HI, we found that miR-30d-5p was one of the most de...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlx052
更新日期:2017-08-01 00:00:00
abstract::Wallerian degeneration of the CNS is accompanied by axonal dystrophy or swelling. To understand the mechanisms by which swellings arise, we studied their spatiotemporal dynamics, ultrastructure, composition, and the conditions that affect their formation in vivo and ex vivo. In contrast to peripheral nerve axons, lesi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181da84db
更新日期:2010-05-01 00:00:00
abstract::Recent studies have shown that the Alzheimer disease (AD) neocortex is characterized by a loss of large neurons, the presence of dilated terminal axons, widespread loss of synapses, and a disruption of the dendritic cytoskeleton which is manifested as Tau immunoreactive threads. In the present study we have investigat...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199207000-00003
更新日期:1992-07-01 00:00:00
abstract::Vascular dementia (VaD) is cognitive decline linked to reduced cerebral blood perfusion, yet there are few therapeutic options to protect cognitive function following cerebrovascular accidents. The purpose of this study was to profile gene expression changes unique to VaD to identify and characterize disease relevant ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlz023
更新日期:2019-05-01 00:00:00
abstract::Lewy bodies and Lewy neurites are the hallmark neuropathologic findings in Parkinson disease, Parkinson disease with dementia, dementia with Lewy bodies, and other alpha-synucleinopathies. They have also been described in the brains of normal older individuals and referred to as incidental Lewy body disease. The purpo...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181ac10a7
更新日期:2009-07-01 00:00:00
abstract::In a series of 126 meningiomas, tumor and patient characteristics were investigated and statistically analyzed. A combined cytogenetic and molecular genetic approach was used to study chromosomal abnormalities and loss of markers on chromosome 22q. This approach was successfully applied to 93 meningiomas. In 66 cases,...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199503000-00009
更新日期:1995-03-01 00:00:00
abstract::Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000052
更新日期:2014-04-01 00:00:00
abstract::β-Amyloid (Aβ) plaques can trigger chronic inflammation in the cellular environment that recruits infiltrating macrophages during the course of Alzheimer disease (AD). Activated macrophages release pro-inflammatory cytokines that increase neurotoxicity associated with AD. A major impediment to investigating neuroinfla...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa093
更新日期:2020-11-01 00:00:00
abstract::Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1. The HTRA1 protein normally represses transforming growth factor-β (TGF-β) signaling and its mutations ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlw078
更新日期:2016-11-01 00:00:00
abstract::To determine whether arterial wall degeneration, in combination with hemodynamic insult, causes cerebral artery aneurysms in a dog model, we simulated the geometry and hemodynamics of a human artery by surgical reconstruction of both common carotid arteries in 12 dogs. The dogs were then randomly assigned to one of th...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000100
更新日期:2014-09-01 00:00:00
abstract::Brainstem Lewy bodies (LB) are neuronal inclusions that are closely related to Parkinson's disease (PD). The filamentous component of LB from patients with PD contains biochemically altered neurofilaments (NF). Herein we have tested the hypothesis that the oxidized products of catechols may covalently crosslink NF. Ne...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199505000-00004
更新日期:1995-05-01 00:00:00
abstract::The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes temozolomide-induced alkylation, thereby preventing DNA damage and cytotoxicity. We investigated the prognostic effect of different MGMT methylation levels on overall and progression-free survival in 327 patients with primary glioblastoma und...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlz032
更新日期:2019-07-01 00:00:00
abstract::Neurofilamentous axonal swellings occur in a number of degenerative and toxic disorders of the nervous system. In one of these, experimental intoxication with beta, beta'-iminodiproprionitrile (IDPN), accumulation of neurofilaments has been shown to result from a defect in slow axonal transport. The consequence of thi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198001000-00004
更新日期:1980-01-01 00:00:00
abstract::Neuroaxonal dystrophy, a distinctive axonopathy characterized by marked enlargement of distal axons, is the hallmark pathologic alteration in aged and diabetic human prevertebral sympathetic ganglia and in corresponding rodent models. Neuroaxonal dystrophy is thought to represent the abnormal outcome of cycles of syna...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318190d6db
更新日期:2008-12-01 00:00:00
abstract::Nemaline myopathy is the most common congenital myopathy and is caused by mutations in various genes such as ACTA1 (encoding skeletal α-actin). It is associated with limb and respiratory muscle weakness. Despite increasing clinical and scientific interest, the molecular and cellular events leading to such weakness rem...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318293b1cc
更新日期:2013-06-01 00:00:00
abstract::Bergmann fibers and the distribution of Golgi epithelial cells were significantly altered in staggerer, reeler and double mutant (affected by both staggerer and reeler conditions). However, the Bergmann fiber anomalies in double mutant were not identical to those of either staggerer or reeler. A comparison of these an...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197705000-00003
更新日期:1977-05-01 00:00:00
abstract::Neoplastic transformation is often associated with aberrant gap junctional intercellular communication. We assessed mutations and expression of the connexin43 (Cx43) gene in 49 intracranial meningiomas. SSCP analyses followed by direct DNA sequencing showed GCG-->GTG (Ala-->Val) transition mutation in codon 253 of the...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta3) in cerebral vessels, has been implicated as a common cause of hemorrhagic stroke and other forms of vascular disease. CAA is also a frequent concomitant of Alzheimer disease (AD). While the longterm consequences of CAA are well recognized from ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000171644.00180.fc
更新日期:2005-07-01 00:00:00