Cortical alpha-synuclein load is associated with amyloid-beta plaque burden in a subset of Parkinson's disease patients.

Abstract:

:Amyloid-beta (Abeta) peptide pathology in Alzheimer's disease (AD) comprises extracellular plaques and cerebral amyloid angiopathy (CAA). In Parkinson's disease (PD), alpha-synuclein forms intraneuronal Lewy bodies (LBs), and cortical LBs are thought to play a major role in cognitive decline designated as PD with dementia. As there is increasing evidence that Abeta may also promote alpha-synuclein fibrillization, we assessed the relationship between LB pathology and Abeta deposition in 40 cases of PD and 20 age-matched controls. In five cortical areas, we established the severity of Abeta plaque load using an approach similar to that recommended by CERAD in AD. LB densities were determined using a morphometric approach. CAA was graded using previously described scales. The APOE genotype was established in 38 PD and 19 control cases. We have found that the overall Abeta plaque burden and, in particular, the diffuse plaque load shows a statistically significant 'large' correlation with the overall cortical LB burden. The strength of this correlation further increases in PD cases (about 50% of the cases) with moderate to high Abeta plaque load. The APOE epsilon4 allele is over-represented in this subgroup. Our data indicate a strong association between pathologically identifiable Abeta plaque burden and alpha-synuclein load in cerebral cortex and provide indirect evidence that Abeta pathology is likely to be an important factor contributing to cognitive decline in a subgroup of PD patients.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Lashley T,Holton JL,Gray E,Kirkham K,O'Sullivan SS,Hilbig A,Wood NW,Lees AJ,Revesz T

doi

10.1007/s00401-007-0336-0

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

417-25

issue

4

eissn

0001-6322

issn

1432-0533

journal_volume

115

pub_type

杂志文章
  • Dendritic synapses of anterior horn neurons in amyotrophic lateral sclerosis: an ultrastructural study.

    abstract::This ultrastructural study deals with the synapses of primary dendrites of the anterior horn neurons in the lower lumbar spinal cords of seven patients with amyotrophic lateral sclerosis (ALS) who had mild neuronal depletion. Specimens from seven age-matched, neurologically normal individuals served as controls. In ea...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050426

    authors: Sasaki S,Iwata M

    更新日期:1996-01-01 00:00:00

  • Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification.

    abstract::Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrP(Sc), and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenot...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-009-0585-1

    authors: Parchi P,Strammiello R,Notari S,Giese A,Langeveld JP,Ladogana A,Zerr I,Roncaroli F,Cras P,Ghetti B,Pocchiari M,Kretzschmar H,Capellari S

    更新日期:2009-11-01 00:00:00

  • High serum creatine kinase levels associated with cylindrical spirals at muscle biopsy.

    abstract::We studied the muscle biopsy from an asymptomatic patient with high serum creatine kinase values. Subsarcolemmal and intermyofibrillar granular inclusions were seen at the light microscopy level. Ultrastructural observation showed clusters of cylindrical spirals (CS). CS are nonspecific, morphological finding, so far ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00318582

    authors: Rapuzzi S,Prelle A,Moggio M,Rigoletto C,Ciscato P,Comi G,Francesca F,Scarlato G

    更新日期:1995-01-01 00:00:00

  • Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis.

    abstract::Abnormal TDP-43 aggregation is a prominent feature in the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Mutations in TARDBP, the gene encoding TDP-43, cause some cases of ALS. The normal function of TDP-43 remains incompletely understood. To better understand TDP-43 biolo...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-010-0659-0

    authors: Kraemer BC,Schuck T,Wheeler JM,Robinson LC,Trojanowski JQ,Lee VM,Schellenberg GD

    更新日期:2010-04-01 00:00:00

  • WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism?

    abstract::Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-007-0231-8

    authors: Mehling M,Simon P,Mittelbronn M,Meyermann R,Ferrone S,Weller M,Wiendl H

    更新日期:2007-08-01 00:00:00

  • Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells.

    abstract::Alpha-synuclein is known to play an important role in several neurodegenerative diseases. Moreover, it is expressed in central nervous system neuronal tumors, and another member of the synuclein family, gamma-synuclein, is overexpressed in breast and ovarian carcinomas. However, the expression of alpha-synuclein has n...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010100443

    authors: Mori F,Inenaga C,Yoshimoto M,Umezu H,Tanaka R,Takahashi H,Wakabayashi K

    更新日期:2002-02-01 00:00:00

  • Cerebellar astrocytoma with extensive lipidization mimicking adipose tissue.

    abstract::We report the case of an elderly woman with a history of headache, vomiting and dizziness while walking. On CT scans a mass was identified in the right cerebellar hemisphere exhibiting radiological characteristics of lipomatous tissue. Surgery revealed a compact lesion consisting of whitish-yellow tissue with a fatty ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00389504

    authors: Walter A,Dingemans KP,Weinstein HC,Troost D

    更新日期:1994-01-01 00:00:00

  • Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat.

    abstract::It is well established that the binding of pathogenic aquaporin-4 (AQP4)-specific autoantibodies to astrocytes may initiate a cascade of events culminating in the destruction of these cells and in the formation of large tissue-destructive lesions typical for patients with neuromyelitis optica spectrum disorders (NMOSD...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-018-1950-8

    authors: Hillebrand S,Schanda K,Nigritinou M,Tsymala I,Böhm D,Peschl P,Takai Y,Fujihara K,Nakashima I,Misu T,Reindl M,Lassmann H,Bradl M

    更新日期:2019-03-01 00:00:00

  • Pericapillary rosettes in the human spinal cord.

    abstract::We have found large eosinophilic bodies in the pericapillary regions of the gray and white matter in the human spinal cord. These are entirely different from the previously reported pericapillary inclusion bodies (PIB). We have designated them pericapillary rosettes (PR), since they consist of clusters of round or ovo...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00299408

    authors: Sasaki S,Maruyama S

    更新日期:1992-01-01 00:00:00

  • Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients.

    abstract::Alzheimer's disease (AD) is a major cause of dementia. Characteristic neuropathological features of AD include neurofibrillary tangles, senile plaques, amyloid angiopathy and microvascular atrophy. The ultra-structure of the microvascular atrophy in AD and its pathogenetic significance have not been defined. This repo...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050386

    authors: Claudio L

    更新日期:1996-01-01 00:00:00

  • mTOR-dependent abnormalities in autophagy characterize human malformations of cortical development: evidence from focal cortical dysplasia and tuberous sclerosis.

    abstract::Focal cortical dysplasia (FCD) is a localized malformation of cortical development and is the commonest cause of severe childhood epilepsy in surgical practice. Children with FCD are severely disabled by their epilepsy, presenting with frequent seizures early in life. The commonest form of FCD in children is character...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-013-1135-4

    authors: Yasin SA,Ali AM,Tata M,Picker SR,Anderson GW,Latimer-Bowman E,Nicholson SL,Harkness W,Cross JH,Paine SM,Jacques TS

    更新日期:2013-08-01 00:00:00

  • Immunological and pathological findings in demyelinating encephalitis associated with canine distemper virus infection.

    abstract::Nine dogs with canine distemper encephalitis (CDE) were examined with immunological techniques including demonstration of antibodies against canine distemper virus (CDV) in the serum and against myelin basic protein (MBP) in serum and in CSF. Mitogen stimulation tests of lymphocytes were also done. The brains were exa...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00691174

    authors: Vandevelde M,Kristensen F,Kristensen B,Steck AJ,Kihm U

    更新日期:1982-01-01 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

    doi:10.1007/s00401-003-0747-5

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

    更新日期:2003-11-01 00:00:00

  • [Enterogenous cyst of the spinal cord associated with mucomyelia (author's transl)].

    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

    authors: Pilz P,Fischbach R,Brenneis M

    更新日期:1977-11-28 00:00:00

  • In vitro synaptotrophic effects of Cerebrolysin in NT2N cells.

    abstract::Recent studies have shown that Cerebrolysin can enhance synaptic function and ameliorate synaptodendritic alterations in animal models of neurodegeneration, suggesting a synaptotrophic effect. We hypothesize that Cerebrolysin might exert this effect, in part, by regulating the expression of amyloid precursor protein (...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010051012

    authors: Mallory M,Honer W,Hsu L,Johnson R,Rockenstein E,Masliah E

    更新日期:1999-05-01 00:00:00

  • Expression of adhesion molecules and monocyte chemoattractant protein -1 (MCP-1) in the spinal cord lesions in HTLV-I-associated myelopathy.

    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

    authors: Umehara F,Izumo S,Takeya M,Takahashi K,Sato E,Osame M

    更新日期:1996-01-01 00:00:00

  • Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI.

    abstract::The close correlation between abnormally low pre-mortem cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ(1-42)) and plaque burden measured by amyloid imaging as well as between pathologically increased levels of CSF tau and the extent of neurodegeneration measured by MRI has led to growing interest in usi...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00401-011-0808-0

    authors: Shaw LM,Vanderstichele H,Knapik-Czajka M,Figurski M,Coart E,Blennow K,Soares H,Simon AJ,Lewczuk P,Dean RA,Siemers E,Potter W,Lee VM,Trojanowski JQ,Alzheimer's Disease Neuroimaging Initiative.

    更新日期:2011-05-01 00:00:00

  • Neuropathological analysis of an adult case of the Cornelia de Lange syndrome.

    abstract::Cornelia de Lange syndrome (CDLS) is a rare multisystemic malformative syndrome of uncertain etiology characterized by severe psychomotor and mental retardation. Here we report the neuropathological analysis of a 35-year-old patient who displayed the classical clinical symptomatology of CDLS. A congenital dysgenesis o...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-002-0562-4

    authors: Vuilleumier N,Kövari E,Michon A,Hof PR,Mentenopoulos G,Giannakopoulos P,Bouras C

    更新日期:2002-09-01 00:00:00

  • Colony stimulating factor-1 potentiates neuronal survival in cerebral cortex ischemic lesion.

    abstract::The effect of the cytokine, colony stimulating factor-1 (CSF-1), on neuronal survival in cerebral cortex ischemic lesion was determined. Ischemic lesions were made in C3H/HeJ mice by disrupting blood vessels that penetrate the cerebral cortex from the pial-vascular plexus. Recombinant human colony stimulating factor 1...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050550

    authors: Berezovskaya O,Maysinger D,Fedoroff S

    更新日期:1996-11-01 00:00:00

  • The distribution of cerebrovascular amyloid in Alzheimer's disease varies with ApoE genotype.

    abstract::We performed a comparative study to assess cerebral amyloid angiopathy and ApoE genotype in cases of Alzheimer's disease (AD). Ten ApoE 3,3 and ten ApoE 4,4 AD brains, as well as ten normal control brains, were selected after matching for age, sex, and duration of disease. Sections of middle frontal and inferior parie...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-006-0162-9

    authors: Trembath D,Ervin JF,Broom L,Szymanski M,Welsh-Bohmer K,Pieper C,Hulette CM

    更新日期:2007-01-01 00:00:00

  • The ontogenesis of Fc gamma receptors and complement receptors CR1 in human peripheral nerve.

    abstract::The ontogenesis of Fc gamma receptors (FcR) and C3b/C4b receptors (CR1) was studied in peripheral nerves from ten fetuses aged from 20 to 38 weeks using immunohistochemical and functional assays. Monoclonal antibodies (mAbs) against FcR and CR1 stained nerve fibers at 10 weeks of gestation and the staining intensity i...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00294219

    authors: Vedeler CA,Scarpini E,Beretta S,Doronzo R,Matre R

    更新日期:1990-01-01 00:00:00

  • Phrenic nerve maturation in the sudden infant death syndrome.

    abstract::It has been suggested that delayed development in either the peripheral or central nervous system could underlie the sudden infant death syndrome (SIDS). We studied the phrenic nerve in an attempt to find if maturation in this nerve was delayed in SIDS, and to see if fiber size differences could explain the paucity of...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050445

    authors: Pamphlett R,Murray N,Louda C

    更新日期:1996-01-01 00:00:00

  • GM1-gangliosidosis in a cross-bred dog confirmed by detection of GM1-ganglioside using electrospray ionisation-tandem mass spectrometry.

    abstract::The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010000187

    authors: Whitfield P,Johnson AW,Dunn KA,Delauche AJ,Winchester BG,Franklin RJ

    更新日期:2000-10-01 00:00:00

  • Distinct distribution of apolipoprotein E and beta-amyloid immunoreactivity in the hippocampus of Parkinson dementia complex of Guam.

    abstract::The distribution of apolipoprotein E (ApoE) was studied in the brain tissue of cases of the amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, locally known as lytico bodig disease (LB), and compared with cases of Alzheimer's disease (AD) and normal brain tissue. In both LB and AD, strong ApoE immuno...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050533

    authors: Schwab C,Steele JC,Akiyama H,McGeer PL

    更新日期:1996-10-01 00:00:00

  • Medulloblastoma subgroups remain stable across primary and metastatic compartments.

    abstract::Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains una...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-015-1389-0

    authors: Wang X,Dubuc AM,Ramaswamy V,Mack S,Gendoo DM,Remke M,Wu X,Garzia L,Luu B,Cavalli F,Peacock J,López B,Skowron P,Zagzag D,Lyden D,Hoffman C,Cho YJ,Eberhart C,MacDonald T,Li XN,Van Meter T,Northcott PA,Haibe-Kain

    更新日期:2015-03-01 00:00:00

  • Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.

    abstract::Multiple system atrophy (MSA) is characterized by the presence of distinctive glial cytoplasmic inclusions (GCIs) within oligodendrocytes that contain the neuronal protein alpha-synuclein (aSyn) and the oligodendroglia-specific phosphoprotein TPPP/p25α. However, the role of oligodendroglial aSyn and p25α in the format...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-019-02014-y

    authors: Mavroeidi P,Arvanitaki F,Karakitsou AK,Vetsi M,Kloukina I,Zweckstetter M,Giller K,Becker S,Sorrentino ZA,Giasson BI,Jensen PH,Stefanis L,Xilouri M

    更新日期:2019-09-01 00:00:00

  • Formation of psammoma bodies in meningocytic whorls. Ultrastructural study and analysis of calcified material.

    abstract::Psammoma bodies in meningocytic whorls were investigated by electron microscopy. In some whorls, connective tissue fibers were seen and membrane-bound vesicles were contiguous to degenerated cells. Some small vesicles, 0.1 to 0.5 micron in diameter, were outlined by plasma membrane (matrix vesicles), other larger ones...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00686081

    authors: Kubota T,Yamashima T,Hasegawa M,Kida S,Hayashi M,Yamamoto S

    更新日期:1986-01-01 00:00:00

  • Regional metabolism of experimental brain tumors.

    abstract::Experimental brain tumors were produced in rats by stereotactical implantation of various neoplastic cell lines (RG 2, RG1 2.2, G 13/11, F 98, RN 6, B 104, and E 367). Using autoradiographic, bioluminescence, and fluoroscopic methods, the following regional hemodynamic and metabolic parameters were measured on intact ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00687050

    authors: Hossmann KA,Mies G,Paschen W,Szabo L,Dolan E,Wechsler W

    更新日期:1986-01-01 00:00:00

  • Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration.

    abstract::Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic f...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-017-1679-9

    authors: Lee EB,Porta S,Michael Baer G,Xu Y,Suh E,Kwong LK,Elman L,Grossman M,Lee VM,Irwin DJ,Van Deerlin VM,Trojanowski JQ

    更新日期:2017-07-01 00:00:00

  • Protein co-expression with axonal injury in multiple sclerosis plaques.

    abstract::Damage to axons in acute multiple sclerosis (MS) lesions is now well established but the mechanisms of this damage remain obscure. Here we have applied a panel of antibodies that identify cell populations and proteins contained in them with a view to detecting those cells and proteins that are localised particularly c...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-006-0045-0

    authors: Diaz-Sanchez M,Williams K,DeLuca GC,Esiri MM

    更新日期:2006-04-01 00:00:00