Abstract:
:In comparison to the levels in age and gender-matched controls, reduced levels of pathological amyloid-β protein in cerebrospinal fluid routinely precede the onset of Alzheimer's disease-related symptoms by several years, whereas elevated soluble abnormal tau fractions (phosphorylated tau, total tau protein) in cerebrospinal fluid are detectable only with the onset and progression of clinical symptoms. This sequence of events in cerebrospinal fluid (amyloid-β changes detectable prior to abnormal tau changes) contrasts with that in which both proteins develop in the brain, where intraneuronal tau inclusions (pretangles, neurofibrillary tangles, neuropil threads) appear decades before the deposition of amyloid-β plaques (diffuse plaques, neuritic plaques). This viewpoint attempts to address questions arising in connection with this apparent sequential discrepancy-questions and issues for which there are currently no clear-cut answers.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Braak H,Zetterberg H,Del Tredici K,Blennow Kdoi
10.1007/s00401-013-1139-0subject
Has Abstractpub_date
2013-11-01 00:00:00pages
631-41issue
5eissn
0001-6322issn
1432-0533journal_volume
126pub_type
杂志文章,评审abstract::Protein aggregation is a major pathological hallmark of many neurodegenerative disorders including polyglutamine diseases. Aggregation of the mutated form of the disease protein ataxin-3 into neuronal nuclear inclusions is well described in the polyglutamine disorder spinocerebellar ataxia type 3 (SCA3 or Machado-Jose...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-010-0717-7
更新日期:2010-10-01 00:00:00
abstract::Wistar rats were given intravenous (i.v.) horseradish peroxidase (HRP) in saline in doses commonly used to study vascular permeability and the blood-brain barrier. Samples of blood were taken from conscious animals via indwelling catheters at intervals up to 6 h after the HRP injection. Plasma concentrations of adreno...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687945
更新日期:1986-01-01 00:00:00
abstract::Using a 3H-labelled virion DNA probe applied to tissue sections, we have previously identified the precise microscopic anatomical location of herpes simplex virus (HSV) during the acute and latent stages of infection of the mouse trigeminal ganglia and central nervous system (CNS). In the present investigation, we com...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00692842
更新日期:1987-01-01 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::Neuroaxonal spheroids became evident microscopically after the autopsy of a 45-year-old woman with pigmentation of the globus pallidus suggesting Hallervorden-Spatz disease. In our opinion the fine floccular pigment seen electron-microscopically in many of the axonal spheroids is melanin, an end product of catecholami...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691981
更新日期:1983-01-01 00:00:00
abstract::Essential mixed cryoglobulinemia, which can cause hypersensitivity vasculitis, was observed in five patients with peripheral neuropathy. Three cases presented with multifocal neuropathies and two cases with symmetrical polyneuropathy. One had cryoglobulinemia with IgM monoclonal gammopathy IgG polyclonal gammopathy, a...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686206
更新日期:1988-01-01 00:00:00
abstract::Electrophysiological studies in subjects with HIV/AIDS demonstrate subtle changes in the visual pathway even in the absence of visual symptoms. But the pathological correlate of the electrophysiological abnormalities is largely unknown. This study attempts to correlate pathological changes in the retina and intraorbit...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-006-0089-1
更新日期:2006-10-01 00:00:00
abstract::New pericapillary inclusion bodies were found in 17 cases of sporadic amyotrophic lateral sclerosis (ALS). The inclusion bodies consisted of paracrystalline arrays with 5-7 nm electron-dense subunits, were discernible with the light microscope and had the staining properties of protein. They were surrounded by capilla...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687970
更新日期:1986-01-01 00:00:00
abstract::The distribution of the calcium-binding protein calretinin was investigated by immunohistochemistry in the hippocampus, the subicular areas, and the entorhinal cortex in patients with Alzheimer's disease and in control subjects. By double immunolabelling, the calretinin immunoreactivity was compared to the immunoreact...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294357
更新日期:1994-01-01 00:00:00
abstract::We have obtained a cDNA fragment to human glial fibrillary acidic protein (GFAP) by immunoscreening a lambda gt11 human brain cDNA library with antibody to bovine GFAP. The highly homologous nucleotide sequence of this clone with that of the mouse GFAP enabled the identification of this cDNA as one encoding GFAP. As t...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687396
更新日期:1989-01-01 00:00:00
abstract::It was earlier shown that bicuculline-induced status epilepticus gives rise to profound acute changes in the rat cerebral cortex, i.e. edema and neuronal alterations. In the present study, we explored to what extent interruption of the seizure activity reverses the changes observed. To that end, status epilepticus of ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00684924
更新日期:1983-01-01 00:00:00
abstract::A human glioma cell line, SA146, was initiated on precoated extracellular matrix from a stereotactic biopsy of a glioblastoma. We report modulation in the expression of glial fibrillary acidic protein (GFAP) by SA146 passed in vitro before or after xenogenic transplantation into nude mice. Immunofluorescence data show...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050722
更新日期:1997-10-01 00:00:00
abstract::Respiratory chain dysfunction leads to reactive oxygen species (ROS) generation with following oxidative stress and cellular damage. A histochemical and immunohistochemical study was performed on muscle biopsies from 17 patients with mitochondrial disease [chronic progressive external ophthalmoplegia (CPEO), mitochond...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010100455
更新日期:2002-03-01 00:00:00
abstract::Patients with von Hippel-Lindau disease carry a germline mutation of the Von Hippel-Lindau (VHL) tumor-suppressor gene. We discuss the molecular consequences of loss of VHL gene function and their impact on the nervous system. Dysfunction of the VHL protein causes accumulation and activation of hypoxia inducible facto...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-013-1091-z
更新日期:2013-03-01 00:00:00
abstract::We investigated whether the brainstem is affected by the pathologic process of sporadic Creutzfeldt-Jakob disease (sCJD), with particular attention to brainstem atrophy, neuronal loss, pyramidal tract degeneration, and prion protein (PrP) deposition, in 33 patients with sCJD. Brainstem atrophy, particularly in the pon...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-0981-0
更新日期:2005-06-01 00:00:00
abstract::We have developed a functional vegetative model by an 18-min clamping of the ascending aorta combined with a bypass formation between the aorta to right atrium and the aorta to femoral vein. Complete global brain ischemia (CGBI) induced for 18 min with this model provided the following distinct advantages: cardiopulmo...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294614
更新日期:1990-01-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have identified several new molecular constituents of ALS-linked cellular aggregates, including FUS, TDP-43, OPTN, UBQLN2 and the translational product...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-013-1125-6
更新日期:2013-06-01 00:00:00
abstract::Round granulated body (RGB) and eosinophilic hyaline droplets (EHDs) have been described as cytoplasmic inclusions of certain astrocytic tumors. In the previous literature, however, these inclusions have been described using various terms or regarded as nosologically the same entity. Light microscopically, RGB appeare...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00296486
更新日期:1994-01-01 00:00:00
abstract::The expression of glial fibrillary acidic protein (GFAP), vimentin, S-100 protein (S-100), HNK-1, myelin basic protein (MBP) and fibronectin was investigated immunohistochemically in 51 ethylnitrosourea (ENU)-induced neurinomas of the rat. Additionally, 90 transplantation tumors derived from ENU-induced neurinomas and...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00310927
更新日期:1991-01-01 00:00:00
abstract::Newborn rats were exposed to daily intraperitoneal injections of 10 mg lead nitrate per kg body weight for the first 15 postnatal days. The growth and mortality of the lead-exposed animals did not differ from their control litter-mates, injected with vehicle only. In our previous studies, focal hemorrhages and spongy ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687071
更新日期:1987-01-01 00:00:00
abstract::Numbers of dystrophic neurites, seen with the electron microscope, in CA1 of the hippocampus of either C3H mice infected with 22C or 79A strains of scrapie, or LM mice infected with strain ME7 were greater than in age-matched control mice. Vacuolation, seen by light microscopy in CA1 of the hippocampus of mice infecte...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688263
更新日期:1987-01-01 00:00:00
abstract::Seven patients aged 29 to 76 years with various clinical subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP) were investigated. Sural nerve biopsies were performed between 7 months and 19 years after onset of disease. Quantitative electron microscopy revealed involvement of primary unmyelinated fibers...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00307700
更新日期:1990-01-01 00:00:00
abstract::Using a fluorescent antibody technique, sections of the brains of patients with senile dementia or Alzheimer's disease containing senile plaques were treated with rabbit antihuman immunoglobulins labelled with FITC (fluorescein isothiocyanate, BBL). The senile plaques and the cerebral amyloid angiopathy (drusige Entar...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00689569
更新日期:1975-08-11 00:00:00
abstract::We describe three cases of early- (cases 1-3, 28-39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinh...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0737-7
更新日期:2003-10-01 00:00:00
abstract::Cystic necrosis in the cerebellar white matter was found in three premature infants. The necrosis was characteristically localized in the center of the white matter of the superficial cerebellar folia, sparing the overlying cortex. The patients were aged between 28 and 34 gestational weeks, and had a clinical history ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00315013
更新日期:1995-01-01 00:00:00
abstract::In looking for a possible influence of nuclear inclusions (NIs) on neurodegeneration in human brains, we quantified morphological features of pontine neurons of three unrelated cases of neuronal intranuclear inclusion disease (NIID) and five control cases. Cross-sectional area of each neuronal nucleus and the indices ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0614-9
更新日期:2003-02-01 00:00:00
abstract::Defective interfering influenza virus particles lessened the yield of infective virus recovered from brain after intracerebral challange of 3-week old mice, but failed to affect the appearance of disease or lethality. In 7-week old mice, the presence of defective interfering influenza virus particles reduced both leth...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00684666
更新日期:1976-03-15 00:00:00
abstract::When 22 members of the BrainNet Europe (BNE) consortium assessed 31 cases with alpha-synuclein (alphaS) immunoreactive (IR) pathology applying the consensus protocol described by McKeith and colleagues in 2005, the inter-observer agreement was 80%, being lowest in the limbic category (73%). When applying the staging p...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-009-0523-2
更新日期:2009-06-01 00:00:00
abstract::This study reports the histological, ultrastructural, and immunocytochemical characteristics of intracytoplasmic eosinophilic inclusion bodies occurring in various types of neurons of the human central nervous system. By light microscopy, the inclusions were brightly eosinophilic, slightly birefringent, and sharply de...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00308960
更新日期:1989-01-01 00:00:00
abstract::Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The mechanism by which expansion of polyglutamine in AR causes muscle atrophy is unknown. Here, we investigated pathological pathways underlying muscle atrophy in SBMA kn...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-016-1550-4
更新日期:2016-07-01 00:00:00