Abstract:
:Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Holleran L,Kim JH,Gangolli M,Stein T,Alvarez V,McKee A,Brody DLdoi
10.1007/s00401-017-1686-xsubject
Has Abstractpub_date
2017-03-01 00:00:00pages
367-380issue
3eissn
0001-6322issn
1432-0533pii
10.1007/s00401-017-1686-xjournal_volume
133pub_type
杂志文章abstract::Leukocyte adhesion molecules to endothelium plays an important role in the pathogenesis of inflammatory diseases, including HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). To help define the role of adhesion molecules in HAM/TSP, we studied the expression of lymphocyte function-associated antige...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050435
更新日期:1996-01-01 00:00:00
abstract::Two experiments were completed in which brains and spinal cords from lambs affected with spongy degeneration of the central nervous system (CNS) were analysed for water, sodium and potassium, as measures of cerebral oedema. In a third experiment, lambs with CNS spongy degeneration were tested for permeability of cereb...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687928
更新日期:1975-01-01 00:00:00
abstract::An analysis is presented of the immunohistological and ultrastructural features in a series of 118 surgically removed pituitary adenomas all of which were studied immunohistologically using antisera to growth hormone (GH), prolactin (PRL) ACTH, beta FSH, beta LH and beta TSH, and 75 of which were studied ultrastructur...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00684914
更新日期:1983-01-01 00:00:00
abstract::We report the case of an 11-year-old male who developed subacute diffuse polyradiculoneuropathy, associated with digestive symptoms and Epstein-Barr virus infection. Parental consanguinity was present. The laboratory findings including bone marrow smear were consistent with hemophagocytic lymphohistiocytosis (HLH). El...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-004-0897-0
更新日期:2004-10-01 00:00:00
abstract::Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensor...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691784
更新日期:1979-10-01 00:00:00
abstract::The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690549
更新日期:1979-08-01 00:00:00
abstract::A 64-year-old woman developed septicemia and a generalized peripheral neuropathy while being ventilated postoperatively. No cause for the neuropathy could be found during life. At autopsy she was found to have infective endocarditis and multifocal inflammatory lesions in the central and peripheral nervous systems, con...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687409
更新日期:1989-01-01 00:00:00
abstract::Massive GGGGCC repeat expansion in the first intron of the gene C9orf72 is the most common known cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Despite its intronic localization and lack of an ATG start codon, the repeat region is translated in all three reading fra...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-013-1189-3
更新日期:2013-12-01 00:00:00
abstract::The diagnosis of infantile neuro-axonal dystrophy (INAD) in a 5-year-old patient was confirmed by the ultrastructural study of neuromuscular, skin and conjunctival biopsy specimens. Abnormal networks of smooth membranous, lamellar and tubular profiles were found in presynaptic terminals and in conjunctival and dermal ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00702677
更新日期:1979-03-15 00:00:00
abstract::Myotubular myopathy and centronuclear myopathies (CNM) are congenital myopathies characterized by generalized muscle weakness and mislocalization of muscle fiber nuclei. Genetically distinct forms exist, and mutations in BIN1 were recently identified in autosomal recessive cases (ARCNM). Amphiphysins have been implica...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-010-0754-2
更新日期:2011-02-01 00:00:00
abstract::In the present work the effect of Piromen is studied on the formation of the glial-mesenchymal scar in the experimentally injuried cortex of hamsters. The uniform effect of the bacterial polysaccharide is suggested in a strong and lasting stimulation of proliferating reactive cells in the traumatic area. The excessive...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00684561
更新日期:1975-01-01 00:00:00
abstract::Foetal rat brain reaggregate cultures have been employed to investigate the morphological changes associated with the neurotoxic action of ethylcholine mustard aziridinium (ECMA). In a companion study we provided evidence for apparent selective cholinergic neurotoxicity. Exposure of 9-day-old cultures to 12.5 microM E...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00334882
更新日期:1993-01-01 00:00:00
abstract::Equine grass sickness (EGS) is an acquired disease of unknown aetiology affecting horses kept at grass. The disease is characterised by postganglionic sympathetic and parasympathetic neuronal pathology and is categorised as a dysautonomia. This study undertook a systematic examination of brain stem cranial nerve nucle...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010000289
更新日期:2001-08-01 00:00:00
abstract::Two types of intranuclear inclusions were described in a brain biopsy from a patient with Creutzfeldt-Jakob disease. The first type of intranculear inclusion was papova virus-like and was observed within 20% of the nuclei of all astrocytes and neurons examined. The particles measured 32 nm in diameter and consisted of...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687930
更新日期:1975-01-01 00:00:00
abstract::The suprascapular nerve from 14 horses, which had no clinical evidence of spinatus muscle atrophy, were obtained to determine whether the nerve was sub-clinically compressed at the scapular edge. The nerves were divided into three portions, proximal and distal to the scapular edge and as it reflected around it. In nin...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688338
更新日期:1987-01-01 00:00:00
abstract::A case of secretory meningioma with numerous meningothelial rosettes is reported. A 66-year-old man with moyamoya disease gradually developed skull deformity, and underwent surgery for the skull tumor overlying the hemisphere. Histological examination disclosed numerous meningothelial rosettes quite similar to those i...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227831
更新日期:1992-01-01 00:00:00
abstract::The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-alpha is to induce astrocyte proliferation in vitro. The...
journal_title:Acta neuropathologica
pub_type: 临床试验,杂志文章
doi:10.1007/s004010050646
更新日期:1997-05-01 00:00:00
abstract::Among the various mechanisms proposed to explain the pathogenesis of cerebral lesions in human immunodeficiency virus (HIV)-induced encephalitis, a cytokine-mediated action has found most favour. Indeed, elevated expression of cytokines such as interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha), thought to...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050457
更新日期:1996-01-01 00:00:00
abstract::This report illustrates a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) masquerading as neurofibromatosis due to multifocal enlargements of spinal nerve roots. The patient initially complained of intermittent numbness of the hands and leg weakness at age 62. Nerve conduction velocities were ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0616-7
更新日期:2003-02-01 00:00:00
abstract::The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of neuromuscular disorders subdivided into polymyositis (PM), sporadic inclusion body myositis (sIBM) and dermatomyositis (DM). Chemokines play an essential role in sustained inflammation associated with IIM. We studied the distribution of the alph...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-0989-5
更新日期:2005-06-01 00:00:00
abstract::Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer's disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-010-0667-0
更新日期:2010-06-01 00:00:00
abstract::Psammoma bodies at the perivascular area in five cases of meningioma were examined with the electron microscope. In general, meningocytic cells invest the outer aspect of blood vessels, which are constituted by multilayered basal laminae, collagen fibers, microfibrils, and pericytes. Remnants of degenerated cells are ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688693
更新日期:1985-01-01 00:00:00
abstract::To clarify the significance of the constituents of canine senile plaques (SPs) or cerebrovascular amyloid deposits, paraffin and cryostat sections of canine brains were examined by immunohistochemistry using antibodies against cathepsin B (CB), cathepsin D (CD), cystatin C (CC), alpha-1-antichymotrypsin (ACT), heat sh...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050615
更新日期:1997-03-01 00:00:00
abstract::The endothelial cells of three cases of cerebellar capillary hemangioblastoma were studied by means of electron microscopy. Crystalloid bodies, not previously described in the vessels of the central nervous system (CNS), were found in 5%-10% of the endothelial cells, more often in the capillaries with small irregular ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688686
更新日期:1985-01-01 00:00:00
abstract::In spite of several cases reported in the literature, the exact pathogenetic mechanism of neuropathic changes in porphyric neuropathy remains uncertain. Various authors have ascribed the neuropathologic findings to either a dying-back axonal degeneration or segmental demyelination. In recent years, the hypothesis of a...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00697191
更新日期:1984-01-01 00:00:00
abstract::The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demon...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00228582
更新日期:1993-01-01 00:00:00
abstract::Histopathological, immunocytochemical, and electron microscopical investigations were carried out in a man with a protracted history of spastic paraparesis, adrenal insufficiency and hypogonadism. Pathological findings were identical with those of the few previously reported cases of adrenomyeloneuropathy (AMN) includ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690750
更新日期:1980-01-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and adult onset X-linked recessive bulbospinal muscular atrophy (SPMA), constituting the category of adult onset form of motor neuron disease, were analyzed on motor nerve roots. The results of morphometric analysis on ventral spinal roots (VSR) of all spinal segments from ALS and S...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691322
更新日期:1981-01-01 00:00:00
abstract::Aggregation and toxicity of the amyloid β-peptide (Aβ) are considered as critical events in the initiation and progression of Alzheimer's disease (AD). Recent evidence indicated that soluble oligomeric Aβ assemblies exert pronounced toxicity, rather than larger fibrillar aggregates that deposit in the forms of extrace...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-016-1546-0
更新日期:2016-04-01 00:00:00
abstract::Gliomatosis cerebri (GC), a rare and deadly CNS neoplasm characterized by involvement of at least three cerebral lobes, predominantly affects adults. While a few small series have reported its occurrence in children, little is known about the molecular characteristics of pediatric GC. We reviewed clinical, radiologica...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-015-1532-y
更新日期:2016-02-01 00:00:00