Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy.


:Neuronal accumulation of oligomeric amyloid-beta (Alphabeta) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Abeta stress to neurons by immigration into the brain and phagocytosis of Alphabeta. We tested migration and export across a blood-brain barrier model, and phagocytosis and clearance of Alphabeta by AD and normal subjects' macrophages. Both AD and normal macrophages were inhibited in Alphabeta export across the blood-brain barrier due to adherence of Abeta-engorged macrophages to the endothelial layer. In comparison to normal subjects' macrophages, AD macrophages ingested and cleared less Alphabeta, and underwent apoptosis upon exposure to soluble, protofibrillar, or fibrillar Alphabeta. Confocal microscopy of stained AD brain sections revealed oligomeric Abeta in neurons and apoptotic macrophages, which surrounded and infiltrated congophilic microvessels, and fibrillar Abeta in plaques and microvessel walls. After incubation with AD brain sections, normal subjects' monocytes intruded into neurons and uploaded oligomeric Abeta. In conclusion, in patients with AD, macrophages appear to shuttle Abeta from neurons to vessels where their apoptosis may release fibrillar Abeta, contributing to cerebral amyloid angiopathy.


Acta Neuropathol


Acta neuropathologica


Zaghi J,Goldenson B,Inayathullah M,Lossinsky AS,Masoumi A,Avagyan H,Mahanian M,Bernas M,Weinand M,Rosenthal MJ,Espinosa-Jeffrey A,de Vellis J,Teplow DB,Fiala M




Has Abstract


2009-02-01 00:00:00












  • Neurotoxicity of monosodium-L-glutamate in pregnant and fetal rats.

    abstract::Monosodium-L-glutamate given subcutaneously to pregnant rats caused acute necrosis of the acetylcholinesterase-positive neurons in the area postrema. The same effect has been observed in the area postrema of fetal rats. The process of neuronal cell death and the elimination of debris by microglia cells proved to be si...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Tóth L,Karcsu S,Feledi J,Kreutzberg GW

    更新日期:1987-01-01 00:00:00

  • Progranulin and frontotemporal lobar degeneration.

    abstract::Frontotemporal lobar degeneration is the term used to describe the non-Alzheimer clinical syndromes of frontotemporal dementia, semantic dementia and progressive non-fluent aphasia, regardless of the underlying neuropathological features. Considerable progress has been made in recent years in our understanding of the ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,评审


    authors: Pickering-Brown SM

    更新日期:2007-07-01 00:00:00

  • Subependymoma: a case report with ultrastructural study.

    abstract::A case history illustrating the potential clinical significance of subependymoma is presented. Fine structural studies indicate that the tumor is composed of cells having the cytoplasmic features of ependyma, astrocytes, and transitional cells. Its composition and structure are alike those in the adult mammalian subep...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Azzarelli B,Rekate HL,Roessmann U

    更新日期:1977-11-28 00:00:00

  • Tumour necrosis factor-mediated cell death pathways do not contribute to muscle fibre death in dystrophinopathies.

    abstract::There is evidence that apoptotic cell death mechanisms contribute to muscle fibre loss in dystrophinopathies, but little knowledge about the activators of the final degrading caspase cascade in muscle fibre apoptosis. As mitochondria-related activation of this caspase cascade, through e.g. APAF-1, could not be proven ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Tews DS

    更新日期:2005-02-01 00:00:00

  • Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells.

    abstract::Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor fro...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Barszczyk M,Buczkowicz P,Castelo-Branco P,Mack SC,Ramaswamy V,Mangerel J,Agnihotri S,Remke M,Golbourn B,Pajovic S,Elizabeth C,Yu M,Luu B,Morrison A,Adamski J,Nethery-Brokx K,Li XN,Van Meter T,Dirks PB,Rutka JT,Tay

    更新日期:2014-12-01 00:00:00

  • CNS T-cell lymphoma: an under-recognized entity?

    abstract::The incidence of CNS lymphoma has increased significantly in the past 30 years, primarily in the elderly and immunocompromised. While T-cell lymphomas comprise 15-20% of systemic lymphomas, they comprise less than 4% of primary CNS lymphomas, suggesting that they may be under-recognized compared to their systemic coun...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Dulai MS,Park CY,Howell WD,Smyth LT,Desai M,Carter DM,Vogel H

    更新日期:2008-03-01 00:00:00

  • N-Hexane- and methylethylketone-induced polyneuropathy. Abnormal accumulation of glycogen in unmyelinated axons. Report of a case.

    abstract::This report presents the ultrastructural nerve study of a patient with sensorimotor neuropathy by a shoe glue containing an association of n-hexane and methylethylketone. Giant axons, distended by microfilamentous proliferation typical of such cases of neuropathy, were found in significant amounts. An unusual histolog...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Vallat JM,Leboutet MJ,Loubet A,Piva C,Dumas M

    更新日期:1981-01-01 00:00:00

  • Morphological evaluation of amyloid-laden arteries in leptomeninges, cortices and subcortices in cerebral amyloid angiopathy with subcortical hemorrhage.

    abstract::To investigate the relationship between cerebral amyloid angiopathy and subcortical (lobar) hemorrhage, we examined the severity of amyloid deposition in the leptomeningeal, cortical and subcortical arteries in 28 autopsied elderly patients with cerebral amyloid angiopathy with subcortical hemorrhage, deep cerebral he...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Iwamoto N,Ishihara T,Ito H,Uchino F

    更新日期:1993-01-01 00:00:00

  • Extrapyramidal features in patients with motor neuron disease and dementia; a clinicopathological correlative study.

    abstract::Motor neuron disease (MND) may be complicated by frontotemporal dementia and/or an extrapyramidal movement disorder. Several studies have identified the pathological substrate for dementia in MND as being ubiquitin-immunoreactive inclusions and dystrophic neurites in the extramotor neocortex and hippocampus. Although ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Mackenzie IR,Feldman H

    更新日期:2004-04-01 00:00:00

  • The vesicular forebrain (pseudo-aprosencephaly): a missing link in the teratogenetic spectrum of the defective brain anlage and its discrimination from aprosencephaly.

    abstract::Two cases out of a sample of 41 fetuses and infants with prosencephalic malformation, observed at the Institute of Pathology and Department of Neuropathology of the University of Heidelberg, are described here in detail. These cases presented grossly with microcephaly and missing forebrain, appearing to be cases of ap...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Sergi C,Schmitt HP

    更新日期:2000-03-01 00:00:00

  • Distribution of prion protein in German patients with Creutzfeldt-Jakob disease is different from that in Japanese patients.

    abstract::We investigated the distribution of prion protein (PrP) in 14 German patients with sporadic Creutzfeldt-Jakob disease (CJD) and compared it with that observed in Japanese patients. Immunohistochemical study revealed diffuse gray matter stainings including synaptic structures in all cases. In addition, 4 patients showe...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Doi-Yi R,Kitamoto T,Ogomori K,Mehraein P,Tateishi J

    更新日期:1994-01-01 00:00:00

  • Hallmark cellular pathology of Alzheimer's disease induced by mutant human tau expression in cultured Aplysia neurons.

    abstract::The mechanisms underlying neurodegenerative diseases are the outcome of pathological alterations of evolutionary conserved molecular and cellular cascades. For this reason, Drosophila and C. elegans serve as useful model systems to study various aspects of neurodegenerative diseases. Here, we introduce the advantageou...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Shemesh OA,Spira ME

    更新日期:2010-08-01 00:00:00

  • The origin, fate, and contribution of macrophages to spinal cord injury pathology.

    abstract::Virtually all phases of spinal cord injury pathogenesis, including inflammation, cell proliferation and differentiation, as well as tissue remodeling, are mediated in part by infiltrating monocyte-derived macrophages. It is now clear that these infiltrating macrophages have distinct functions from resident microglia a...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,评审


    authors: Milich LM,Ryan CB,Lee JK

    更新日期:2019-05-01 00:00:00

  • Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG).

    abstract::X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located on Xp22.13. Arx-null mice show loss of tangential migration of GABAergic interneurons, presumably being related to caudal ganglionic eminence tangential migration. In the ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Okazaki S,Ohsawa M,Kuki I,Kawawaki H,Koriyama T,Ri S,Ichiba H,Hai E,Inoue T,Nakamura H,Goto Y,Tomiwa K,Yamano T,Kitamura K,Itoh M

    更新日期:2008-10-01 00:00:00

  • Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord.

    abstract::We evaluated by in situ nick end labeling the presence of apoptotic glial cells in the spinal cord of rats which have sustained a moderate and severe compression injury at the level of T8-9, resulting in a severe but reversible paraparesis and irreversible paraplegia, respectively. In a previous investigation we found...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Li GL,Farooque M,Holtz A,Olsson Y

    更新日期:1999-11-01 00:00:00

  • Unilateral hemispheric cerebral changes similar to Creutzfeldt-Jakob disease in a case of hemiconvulsion.

    abstract::A 77-year-old man suffered intermittent hemiconvulsions of unknown etiology on the left side for a period of about 5 weeks. At the autopsy, there was marked neuronal loss, severe proliferation of astrocytes and spongiform changes in the right cerebral cortex. The cerebral white matter showed loosening with astroglial ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Yamanouchi H,Matsui R,Tomonaga M,Sakurai H,Yoshimura M,Shimada H

    更新日期:1988-01-01 00:00:00

  • Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue.

    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


    authors: Knappe UJ,Hagel C,Lisboa BW,Wilczak W,Lüdecke DK,Saeger W

    更新日期:2003-11-01 00:00:00

  • The fine structure of cerebral capillaries in "overgrown" neural tissue.

    abstract::Cerebral capillaries in "overgrown" neural tissue of chick embryo brains ranging in age from 5-18 days of incubation were studied by means of electron microscopy. The vessels in the abnormal tissue showed more extensive and prolonged interdigitations and overlapping of adjacent endothelial cells than did those in norm...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Wilson DB,Finta LA,Bois RM

    更新日期:1979-04-12 00:00:00

  • Lesions of excitatory pathways reduce hippocampal cell death after transient forebrain ischemia in the gerbil.

    abstract::Transient forebrain ischemia produces a spatially and temporally selective pattern of neuronal degeneration in the hippocampal formation of the Mongolian gerbil. Ischemic neuronal death has been suggested to depend on the activation of excitatory hippocampal pathways that project to the vulnerable neurons. This idea w...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Kaplan TM,Lasner TM,Nadler JV,Crain BJ

    更新日期:1989-01-01 00:00:00

  • Neuronopathic juvenile glucosylceramidosis due to sap-C deficiency: clinical course, neuropathology and brain lipid composition in this Gaucher disease variant.

    abstract::Glucosylceramide lipidosis results from a defective lysosomal degradation of this glycolipid. Lipid degradation is controlled by two components, the enzyme beta-glucocerebrosidase and a sphingolipid activator protein. While most Gaucher cases are due to mutations within the gene that codes for the lysosomal enzyme, on...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Pàmpols T,Pineda M,Girós ML,Ferrer I,Cusi V,Chabás A,Sanmarti FX,Vanier MT,Christomanou H

    更新日期:1999-01-01 00:00:00

  • Alanine formation and alanine aminotransferase activity in the nerve tissue with proliferating macroglia.

    abstract::In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate s...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Ruscák M,Hager H,Orlický J

    更新日期:1976-03-15 00:00:00

  • A novel leukoencephalopathy associated with tau deposits primarily in white matter glia.

    abstract::A 79-year-old woman had a 10-year history of dementia, initially presenting as non-fluent aphasia. Magnetic resonance imaging showed frontal atrophy (left greater than right) and hyperintense foci within white matter. Neuropathologically, there was severe frontal atrophy due to cortical neuronal loss with spongy chang...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Powers JM,Byrne NP,Ito M,Takao M,Yankopoulou D,Spillantini MG,Ghetti B

    更新日期:2003-08-01 00:00:00

  • Reappraisal of progressive multifocal leukoencephalopathy due to simian virus 40.

    abstract::Several cases of progressive multifocal leukoencephalopathy (PML) have been associated with simian virus 40 (SV40), rather than with JC virus (JCV), the polyomavirus originally isolated from PML tissue. PML has, therefore, been defined as a demyelinating syndrome with possible multiple viral etiologies. Tissues from t...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Stoner GL,Ryschkewitsch CF

    更新日期:1998-09-01 00:00:00

  • Primary parafalcine chondrosarcoma in a child.

    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


    authors: Gerszten PC,Pollack IF,Hamilton RL

    更新日期:1998-01-01 00:00:00

  • Neurofibrillary accumulation in the zebra (Equus burchelli).

    abstract::Two young zebra siblings from consecutive pregnancies suffered from neurological disease, characterized by ventral deviation of the neck and tetraparesis which progressed to tetraplegia within a few weeks. On histological examination widespread neuronal degeneration was observed in the ventral horns of the spinal cord...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Higgins RJ,Vandevelde M,Hoff EJ,Jagar JE,Cork LC,Silberman MS

    更新日期:1977-01-31 00:00:00

  • Establishment and characterization of 5 human cell lines derived from a series of 50 primary intracranial tumors.

    abstract::A series of 50 human primary intracranial tumors were cultivated in vitro in an attempt to establish cell lines with the trypsinization technique. During the in vitro adaptation period, cultures were maintained at high cell density to avoid rapid over-growth by connective tissue. Five lines were established from 5 tum...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Maunoury R

    更新日期:1977-07-15 00:00:00

  • Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors.

    abstract::We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Guo D,Nilsson J,Haapasalo H,Raheem O,Bergenheim T,Hedman H,Henriksson R

    更新日期:2006-03-01 00:00:00

  • Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex.

    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


    authors: Seilhean D,Kobayashi K,He Y,Uchihara T,Rosenblum O,Katlama C,Bricaire F,Duyckaerts C,Hauw JJ

    更新日期:1997-05-01 00:00:00

  • Colocalization of cholinesterases with beta amyloid protein in aged and Alzheimer's brains.

    abstract::The colocalization of beta amyloid protein with the enzymes acetyl- and butyrylcholinesterase was assessed using immunocytochemistry for beta amyloid protein and a sensitive histochemical technique for cholinesterases. In non-demented aged and Alzheimer's disease brains, double-stained sections for cholinesterases and...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Morán MA,Mufson EJ,Gómez-Ramos P

    更新日期:1993-01-01 00:00:00

  • Changes in the cytoskeletal proteins, sarcoplasmic reticulum, and capillaries in acute relaxant-steroid myopathy (ARSM) in contrast to the corticosteroid myopathy.

    abstract::Since we reported a case of acute relaxant-steroid myopathy (ARSM) in 1994, we continued histological studies and compared the findings with those in a case of corticosteroid myopathy (CM). It was revealed that (1) dystrophin, spectrin, beta dystroglycan, and sarcoglycans on the cell surface were decreased, (2) regula...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Matsubara S,Kitaguchi T,Isozaki E,Miyamoto K,Hirai S

    更新日期:1999-05-01 00:00:00