Abstract:
:The amyloid cascade hypothesis of Alzheimer's disease (AD) is testable: it implies that interference with Abeta aggregation and plaque formation may be therapeutically useful. Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques. The first clinical studies of Abeta immunisation in AD patients (AN1792, Elan Pharmaceuticals) were halted when some patients suffered side effects. Since our confirmation that Abeta immunisation can prompt plaque removal in human AD, we have performed a clinical and neuropathological follow up of AD patients in the initial Elan Abeta immunisation trial. In immunised AD patients, we found: a lower Abeta load, with evidence that plaques had been removed; a reduced tau load in neuronal processes, but not in cell bodies; and no evidence of a beneficial effect on synapses. There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta. A pathophysiological mechanism involving effects on the cerebral vasculature is proposed for the clinical side effects observed with some active and passive vaccine protocols. Our current knowledge of the effects of Abeta immunotherapy is based on functional information from the early clinical trials and a few post mortem cases. Several further clinical studies are underway using a variety of protocols and important clinical, imaging and neuropathological data will become available in the near future. The information obtained will be important in helping to understand the pathogenesis not only of AD but also of other neurodegenerative disorders associated with protein aggregation.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Boche D,Denham N,Holmes C,Nicoll JAdoi
10.1007/s00401-010-0719-5subject
Has Abstractpub_date
2010-09-01 00:00:00pages
369-84issue
3eissn
0001-6322issn
1432-0533journal_volume
120pub_type
杂志文章,评审abstract::Marinesco-Sjögren syndrome (MSS) features cerebellar ataxia, mental retardation, cataracts, and progressive vacuolar myopathy with peculiar myonuclear alterations. Most MSS patients carry homozygous or compound heterozygous SIL1 mutations. SIL1 is a nucleotide exchange factor for the endoplasmic reticulum resident cha...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-013-1224-4
更新日期:2014-05-01 00:00:00
abstract::A desmoplastic primary cerebral neuroblastoma originating in the frontal lobe of a boy who died at the age of 6 years contained dense core vesicles within the cytoplasm of neoplastic cells as evidence of neuronal differentiation. Sarcomatous transformation had occurred at the time of recurrence. At autopsy, he also ha...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688540
更新日期:1980-01-01 00:00:00
abstract::Neurons of Area 11 in the fronto-orbital cortex of 18 unselected AIDS brains are analyzed by means of stereology. Neurological abnormalities including dementing symptoms were described in eight patients. Neuropathology diagnosed human immunodeficiency virus (HIV)-specific changes in four, and diffuse poliodystrophy in...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294228
更新日期:1990-01-01 00:00:00
abstract::We examined the effect of lactic acid on cultured human glioma cell lines expressing glial fibrillary acidic protein (GFAP), vimentin and neuron-specific enolase (NSE). The growth of the cells was inhibited by the lactic acid in a dose-dependent manner. At 56 mM of lactic acid, the surviving cells of the KNS-42-c2 cel...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00296110
更新日期:1990-01-01 00:00:00
abstract::The evolvement of amyloid beta (Abeta) deposition in the frontal cerebral cortex of 24 patients of increasing age with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) was studied using end-specific monoclonal antibodies to Abetax-42 (Abeta42) or Abetax-40 (Abeta40) and markers for degenerating neu...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010051143
更新日期:2000-04-01 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::Mutations in the sarcomeric protein titin, encoded by TTN, are emerging as a common cause of myopathies. The diagnosis of a TTN-related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and the prevalence of TTN variants in control populations. Here, we present a...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-020-02257-0
更新日期:2021-01-15 00:00:00
abstract::Seven patients with the typical clinical picture and muscle biopsy findings of classical Werdnig-Hoffmann disease showed Wallerian degeneration in their biopsied sural nerves. In dorsal root ganglia of one patient there were residual nodules and several chromatolytic neurons. By electron microscopy the changes of chro...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690973
更新日期:1978-05-24 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::A 40-year-old man suffering from amyotrophic lateral sclerosis with symmetrical degeneration of the thalamus and the substantia nigra is reported. The distribution pattern of the thalamic degeneration in the present case was characteristic in that the Nucleus centralis was the severest affected of the thalamic nuclei...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691074
更新日期:1978-12-15 00:00:00
abstract::The regional distribution of the postsynaptic microtubule-associated protein 2 (MAP2) and the presynaptic marker protein synaptophysin was investigated by immunohistochemistry in brains of rats submitted to 30-min forebrain ischemia by four-vessel occlusion. The following brain temperature profiles during ischemia wer...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00230493
更新日期:1993-01-01 00:00:00
abstract::The cytoskeletal properties and endogenous degradation of intermediate filaments in cultured human glioma cells (U-251MG) were studied using monoclonal antibodies in immunohistochemical and immunochemical methods. Both glial fibrillary acidic protein (GFAP)- and vimentin-antibodies gave a fibrillar cytoplasmic stainin...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687041
更新日期:1986-01-01 00:00:00
abstract::Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). Serine proteases have not yet been investigated in human pituitary adenomas. In this study, paraffin-embedded material from 84 human pituitary adenomas (acromegaly n=18, Cushing's dise...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0747-5
更新日期:2003-11-01 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::The deficiency of the cholinergic cortical projection system arising in the different basal forebrain structures collectively referred to as nucleus basalis of Meynert complex is a constant finding in Alzheimer's disease, a disorder which is neuro-pathologically characterised by the appearance of three intracerebral f...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690530
更新日期:1988-01-01 00:00:00
abstract::Intracranial solitary fibrous tumors (SFTs) are typically dural-based, CD34-positive neoplasms of uncertain histogenesis. We examined ten cases of meninges obtained at autopsy from patients with no history of neurological illness, head trauma, or neurosurgical intervention, and ten cases of typical meningiomas with at...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010100389
更新日期:2001-10-01 00:00:00
abstract::The effects of ageing, cachexia and neoplasms on striated muscle were examined in histological sections of an autopsy material. Paraffin sections were examined from four separate muscles of 30 previously healthy subjects who died suddenly, from eight cases with cachexia and from 16 cases with cachexia and neoplasms. I...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685374
更新日期:1982-01-01 00:00:00
abstract::Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials target...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-012-0952-1
更新日期:2012-07-01 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::Interstitial cells are isolated neurons located in the infracortical white matter that are known to express neuropeptides. Twenty-four cases selected for the absence, slight (Braak stages I-II), moderate (Braak stages III-IV), or serious degree (Braak stages V-VI) of cortical neurofibrillary pathology were studied for...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0551-7
更新日期:2002-10-01 00:00:00
abstract::A woman of 22 years developed heavy pain in the neck and arms with weakness and paresthesia. She died two days after a myelography which was normal. At autopsy an enterogenous extra- and intra-medullary cyst of the cervical cord (C3, C4) was found. In addition the cervical cord apart from the cyst and the uppermost th...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691967
更新日期:1977-11-28 00:00:00
abstract::We described a new type of cytoplasmic inclusion in the choroidal epithelial cells of humans. The inclusions usually appeared as brown, round or elongated bodies with or without an inner core, ranging in size from 1.3 to 7.0 micron. Histochemically, they contained polysaccharides, proteins and compound lipids. Ultrast...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687675
更新日期:1988-01-01 00:00:00
abstract::Ubiquitin-positive Lewy neurites and Lewy bodies are found in idiopathic Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). We found that, in three patients with PD and one with DLBD, microtubule-associated protein 5 (MAP5) immunostaining was consistently present in both Lewy neurites and Lewy bodies throu...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050395
更新日期:1996-01-01 00:00:00
abstract::3-Nitropropionic acid (NPA), a toxin which irreversibly inhibits the Krebs cycle enzyme succinate dehydrogenase, causes severe neurologic disease and a specific pattern of morphologic brain damage when given subcutaneously to rats. To determine whether hypotension or hypoxemia were necessary for development of morphol...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688340
更新日期:1987-01-01 00:00:00
abstract::The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-012-1002-8
更新日期:2012-10-01 00:00:00
abstract::Intracranial cartilaginous tumors are rare lesions, usually arising from the skull base in older individuals. We report the case of a 12-year-old girl with a low-grade type chondrosarcoma arising from the falx cerebri. To our knowledge this is the first such case reported in a child. She was treated with gross total s...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050773
更新日期:1998-01-01 00:00:00
abstract::Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-015-1521-1
更新日期:2016-02-01 00:00:00
abstract::Histological, immunohistochemical and ultrastructural sural nerve and skin biopsy findings in a case of cryoglobulinemia secondary to an IgM-kappa-producing non-Hodgkin lymphoma are described. The main finding was an occlusive microangiopathy present in both the sural nerve and the skin. Widespread cryoglobulin deposi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00713536
更新日期:1992-01-01 00:00:00
abstract::We studied three siblings and one unrelated patient with cerebrotendinous xanthomatosis (CTX). Of two unrelated patients, we examined biopsies of sural nerve, soleus muscle, and achilles tendon. We also performed neurophysiologic investigations. Another patient died, and a postmortem examination of both brain and spin...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688117
更新日期:1984-01-01 00:00:00
abstract::A complex neuropathological study of two cases of Niemann-Pick disease (NPD) type C (NPDC) revealed some novel features in the chemical pathology of the neuronal storage. Lipid histochemistry showed the presence of a lipid which met the criteria of a neuronal glycosphingolipid. Sphingomyelin (SM) was not detected in t...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690966
更新日期:1985-01-01 00:00:00