共查询到20条相似文献,搜索用时 15 毫秒
1.
Jon B. Toledo Pallavi Gopal Kevin Raible David J. Irwin Johannes Brettschneider Samantha Sedor Kayla Waits Susana Boluda Murray Grossman Vivianna M. Van Deerlin Edward B. Lee Steven E. Arnold John E. Duda Howard Hurtig Virginia M.-Y. Lee Charles H. Adler Thomas G. Beach John Q. Trojanowski 《Acta neuropathologica》2016,131(3):393-409
2.
Thomas G. Beach Charles H. Adler Lucia I. Sue Linda Vedders LihFen Lue Charles L. White III Haru Akiyama John N. Caviness Holly A. Shill Marwan N. Sabbagh Douglas G. Walker 《Acta neuropathologica》2010,119(6):689-702
A sensitive immunohistochemical method for phosphorylated α-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson’s disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer’s disease with Lewy bodies (ADLB) and 17 with Alzheimer’s disease with no Lewy bodies (ADNLB). The relative densities and frequencies of occurrence of phosphorylated α-synuclein histopathology (PASH) were tabulated and correlated with diagnostic category. The greatest densities and frequencies of PASH occurred in the spinal cord, followed by the paraspinal sympathetic ganglia, the vagus nerve, the gastrointestinal tract and endocrine organs. The frequency of PASH within other organs and tissue types was much lower. Spinal cord and peripheral PASH was most common in subjects with PD and DLB, where it appears likely that it is universally widespread. Subjects with ILBD had lesser densities of PASH within all regions, but had frequent involvement of the spinal cord and paraspinal sympathetic ganglia, with less-frequent involvement of end-organs. Subjects with ADLB had infrequent involvement of the spinal cord and paraspinal sympathetic ganglia with rare involvement of end-organs. Within the gastrointestinal tract, there was a rostrocaudal gradient of decreasing PASH frequency and density, with the lower esophagus and submandibular gland having the greatest involvement and the colon and rectum the lowest. 相似文献
3.
Satoshi Yamashita Naomi Sakashita Taro Yamashita Nozomu Tawara Masayoshi Tasaki Kensuke Kawakami Yoshihiro Komohara Yukio Fujiwara Masashi Kamikawa Takenobu Nakagawa Teruyuki Hirano Yasushi Maeda Masato Hasegawa Motohiro Takeya Yukio Ando 《Journal of neurology》2014,261(11):2209-2217
Pathological changes in corticobasal degeneration (CBD) consist of abnormal deposition of the microtubule-associated protein tau. However, the simultaneous accumulation of different misfolded proteins in the brain can be observed in many neurodegenerative diseases with significantly longer disease durations. We encountered a patient with CBD who survived for an extremely long period (18 years) after the diagnosis. We performed an autopsy to elucidate the effect of the longer survival on the pathology of CBD. We observed abnormal aggregation of trans-activating response region DNA-binding protein of 43 kDa (TDP-43) and α-synuclein, as well as phosphorylated tau, in neurons of broader regions of the brain, beyond the amygdala and other limbic areas. We found that phosphorylated tau, α-synuclein, and TDP-43 partially co-existed in the same cellular aggregates. The triple pathologic changes might be related to the longer survival of the patient compared with the typical clinical course of patients with CBD. Further investigations are required to support the hypothesis that tauopathy, synucleinopathy, and TDP-43 proteinopathy might share common pathogenic mechanisms in terms of cross-seeding of the pathologic proteins. 相似文献
4.
Hashimoto M Kawahara K Bar-On P Rockenstein E Crews L Masliah E 《Journal of molecular neuroscience : MN》2004,24(3):343-352
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are members of a family of disorders characterized by the presence
of inclusion bodies, or Lewy bodies (LBs), filled with aggregates of α-synuclein. These diseases are a leading cause of movement
disorders and dementia in the aging population, and it is crucial to understand the factors leading to the accumulation and
assembly of these α-synuclein aggregates. Previous studies have uncovered much about the factors leading to aggregation and
the mechanisms causing neurotoxicity of these inclusion bodies; however, little is known about factors that promote the degradation
and prevent the aggregation of α-synuclein. The present article provides a review of recent efforts in the investigation of
factors involved in α-synuclein metabolism and the mechanisms involved in preventing accumulation of α-synuclein and degrading
this molecule. Understanding these processes might provide targets for the development of novel therapies for disorders such
as DLB and PD. 相似文献
5.
Lewy body pathology in Alzheimer’s disease 总被引:2,自引:0,他引:2
Lewy bodies, the characteristic pathological lesion of substantia nigra neurons in Parkinson's disease (PD), are frequently observed to accompany the amyloid plaque and neurofibrillary tangle pathology of Alzheimer's disease (AD). However the typical anatomic distribution of Lewy bodies in AD is distinct from PD. The most common site of occurrence is the amygdala, where Lewy bodies are observed in approximately 60% of both sporadic and familial AD. Other common sites of occurrence include the periamygdaloid and entorhinal cortex, while neocortical and brainstem areas develop Lewy bodies in a lower percentage of cases. In contrast, dementia with Lewy bodies (DLB), defined by widespread neocortical and brainstem Lewy bodies but frequently accompanied by variable levels of AD-type pathology, represents the other end of a spectrum of pathology associated with dementia. The observation of Lewy bodies in familial AD cases suggests that like neurofibrillary tangles, the formation of Lewy bodies can be induced by the pathological state caused by Abeta-amyloid overproduction. The role of Lewy body formation in the dysfunction and degeneration of neurons remains unclear. The protein alpha-synuclein appears to be an important structural component of Lewy bodies, an observation spurred by the discovery of point mutations in the alpha-synuclein gene linked to rare cases of autosomal dominant PD. Further investigation of alpha-synuclein and its relationship to pathological conditions promoting Lewy body formation in AD, PD, and DLB may yield further insight into pathogenesis of these diseases. 相似文献
6.
Keith A. Josephs Melissa E. Murray Jennifer L. Whitwell Joseph E. Parisi Leonard Petrucelli Clifford R. Jack Ronald C. Petersen Dennis W. Dickson 《Acta neuropathologica》2014,127(3):441-450
TDP-43 immunoreactivity occurs in 19–57 % of Alzheimer’s disease (AD) cases. Two patterns of TDP-43 deposition in AD have been described involving hippocampus (limbic) or hippocampus and neocortex (diffuse), although focal amygdala involvement has been observed. In 195 AD cases with TDP-43, we investigated regional TDP-43 immunoreactivity with the aim of developing a TDP-43 in AD staging scheme. TDP-43 immunoreactivity was assessed in amygdala, entorhinal cortex, subiculum, hippocampal dentate gyrus, occipitotemporal, inferior temporal and frontal cortices, and basal ganglia. Clinical, neuroimaging, genetic and pathological characteristics were assessed across stages. Five stages were identified: stage I showed scant-sparse TDP-43 in the amygdala only (17 %); stage II showed moderate-frequent amygdala TDP-43 with spread into entorhinal and subiculum (25 %); stage III showed further spread into dentate gyrus and occipitotemporal cortex (31 %); stage IV showed further spread into inferior temporal cortex (20 %); and stage V showed involvement of frontal cortex and basal ganglia (7 %). Cognition and medial temporal volumes differed across all stages and progression across stages correlated with worsening cognition and medial temporal volume loss. Compared to 147 AD patients without TDP-43, only the Boston Naming Test showed abnormalities in stage I. The findings demonstrate that TDP-43 deposition in AD progresses in a stereotypic manner that can be divided into five distinct topographic stages which are supported by correlations with clinical and neuroimaging features. Given these findings, we recommend sequential regional TDP-43 screening in AD beginning with the amygdala. 相似文献
7.
Ozlem Goker-Alpan Barbara K. Stubblefield Benoit I. Giasson Ellen Sidransky 《Acta neuropathologica》2010,120(5):641-649
Pilocytic astrocytoma (PA) is the most common glioma in the pediatric population. PAs can exhibit variable behavior that does
not always correlate with location. Although oncogenic rearrangements of the BRAF gene have recently been described in PAs, it is not clear whether such alterations have an impact on outcome. An institutional
cohort of 147 PAs (118 with outcome data) from both cerebellar and non-cerebellar locations (spine, diencephalon, midbrain,
brainstem, and cortex) was utilized in this study. Parameters included quantification of characteristic morphologic variables
as well as genes and molecular loci previously shown to be of relevance in high-grade gliomas, including 1p, 9p, 10q, 17p,
19q, and BRAF. Neither 1p, 9p, and 10q nor 19q showed significant association with outcome in PAs, although p16 deletion was more common
in PAs of the midbrain, brainstem, and spinal cord. Loss of heterozygosity on 17p13 correlated with increased risk of recurrence
in cerebellar tumors. BRAF gene rearrangements were more common in cerebellar tumors than non-cerebellar tumors and associated with classic biphasic
histology in the cerebellum. However, clinical outcome was independent of BRAF status. The molecular biology of PAs differs according to location, yet BRAF rearrangements do not appear to produce PAs with different behavior. Nevertheless, such tumors may have altered sensitivity
to pathway-specific adjuvant therapy. Additionally, deletion on 17p13 may be an adverse prognostic biomarker in cerebellar
tumors. 相似文献
8.
Kunikazu Tanji Fumiaki Mori Junsei Mimura Ken Itoh Akiyoshi Kakita Hitoshi Takahashi Koichi Wakabayashi 《Acta neuropathologica》2010,120(2):145-154
Abnormally modified α-synuclein is a pathological hallmark of Parkinson’s disease and the other α-synucleinopathies. Since proteinase K (PK) treatment is known to enhance the immunoreactivity of abnormal α-synuclein, we immunohistochemically examined the brain of transgenic (Tg) mice expressing human mutant A53T α-synuclein using this retrieval method. PK treatment abolished the immunoreactivity of α-synuclein in abnormal inclusions as well as of endogenous α-synuclein in Tg mice, whereas PK-resistant α-synuclein was found in the presynaptic nerve terminals, especially in the hippocampus and temporal cortex. In human Lewy body disease, PK-resistant α-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant α-synuclein was detected in the presynaptic fraction in Tg mice and human Lewy body disease. Although PK-resistant α-synuclein was found in the presynapse in Tg mice even at 1 week of age, it was not phosphorylated until at least 8 months of age. Moreover, PK-resistant α-synuclein in the presynapse was not phosphorylated in human Lewy body disease. These findings suggest that phosphorylation is not necessary to cause the conversion of soluble form to PK-resistant α-synuclein. Considering that native α-synuclein is a soluble protein localized to the presynaptic terminals, our findings suggest that PK-resistant α-synuclein may disturb the neurotransmission in α-synucleinopathies. 相似文献
9.
Kelly Del Tredici Christopher H. Hawkes Estifanos Ghebremedhin Heiko Braak 《Acta neuropathologica》2010,119(6):703-713
A retrospective autopsy-based study of the human submandibular gland, one of the three major salivary glands, together with
anatomically related peripheral structures (cervical superior ganglion, cervical sympathetic trunk, vagal nerve at the level
of the carotid bifurcation), was conducted on a cohort consisting of 33 individuals, including 9 patients with neuropathologically
confirmed Parkinson’s disease (PD), three individuals with incidental Lewy body disease (iLBD), 2 individuals with neuropathologically
confirmed multiple system atrophy (MSA), and 19 controls, using α-synuclein immunohistochemistry in 100 μm polyethylene glycol-embedded
tissue sections. Lewy pathology (LP) was present in the submandibular glands and cervical superior ganglia in PD (9/9 cases)
and iLBD (2/3 cases) but not in MSA or controls. The cervical sympathetic trunk (7/9 PD cases, 2/3 iLBD cases) and peripheral
vagal nerves (9/9 PD cases, 2/3 iLBD cases) also displayed LP. The results are discussed within the context of hyposmia as
well as autonomic dysfunction in PD (sialorrhea, sialopenia, dysphagia). Potential disease-related changes in salivary volume,
contents, and viscosity might make it possible, in combination with other tests, to employ human saliva as a biomarker. 相似文献
10.
Staging/typing of Lewy body related α-synuclein pathology: a study of the BrainNet Europe Consortium
Irina Alafuzoff Paul G. Ince Thomas Arzberger Safa Al-Sarraj Jeanne Bell Istvan Bodi Nenad Bogdanovic Orso Bugiani Isidro Ferrer Ellen Gelpi Stephen Gentleman Giorgio Giaccone James W. Ironside Nikolaos Kavantzas Andrew King Penelope Korkolopoulou Gábor G. Kovács David Meyronet Camelia Monoranu Piero Parchi Laura Parkkinen Efstratios Patsouris Wolfgang Roggendorf Annemieke Rozemuller Christine Stadelmann-Nessler Nathalie Streichenberger Dietmar R. Thal Hans Kretzschmar 《Acta neuropathologica》2009,117(6):635-652
11.
Kurt A. Jellinger 《Acta neuropathologica》2009,118(3):371-379
Postencephalitic parkinsonism (PEP), a chronic complication of encephalitis lethargica, is a tauopathy characterized by multisystem
neuronal loss and gliosis with widespread neurofibrillary lesions composed of both 3- and 4-repeat (3R and 4R) tau isoforms.
Previous immunohistochemical studies in a small number of PEP cases demonstrated absence of Lewy bodies as well as the lack
of other α-synuclein pathology, classifying PEP as a “pure” tauopathy. Neuropathologic examination of 10 brains with clinico-pathologically
verified PEP confirmed widespread neurodegeneration in subcortical and brainstem areas associated with multifocal neurofibrillary
pathology comprising both 3R and 4R tau. Very rare β-amyloid deposits were observed in two elderly patients, while Lewy bodies
and neurites or any other α-synuclein deposits were completely absent. The causes and molecular background of total absence
of α-synuclein pathology in PEP, in contrast to most other tauopathies, remain as unknown as the pathogenesis of PEP. 相似文献
12.
van de Berg WD Hepp DH Dijkstra AA Rozemuller JA Berendse HW Foncke E 《Parkinsonism & related disorders》2012,18(Z1):S28-S30
Parkinson's disease (PD) is characterized by a gradual accumulation of neuropathology that may begin many years before a clinical diagnosis can be made using currently accepted criteria. Here, we first review the prevalence of α-synuclein neuropathology in elderly and discuss its clinical relevance in Parkinson patients. Subsequently, the results of a retrospective study focussing on the distribution of neuropathology in Parkinson patients with a tremor-dominant (TD), non-tremordominant (NTD) or rapid disease progression (RDP) subtype are presented. The study population recruited by the Netherlands Brain bank consisted of 149 non-neurological donors, 26 donors with incidental Lewy body disease (iLBD) and 111 Parkinson patients. In total, 89% of these cases could be classified in accordance with the Braak staging when taking into account the severity of α-synuclein pathology and adding an amygdala-predominant category of synucleinopathy. The pathological progression seemed to be non-linear. Interestingly, a strong correlation between neuronal loss and α-synuclein pathology was observed in the substantia nigra in Braak stages 3-6 (P < 0.01). However, there was no correlation between Hoehn & Yahr and Braak stages. Neuropathological progression may, however, vary between subtypes as cortical Lewy body load and Braak stages were higher in patients with NTD compared to TD and Alzheimer pathology was more prevalent in RDP patients. Recognition of clinical subtypes in neuropathological studies is essential to identify selective vulnerability to protein accumulation that may determine the clinical phenotype in PD. 相似文献
13.
Walter J. Schulz-Schaeffer 《Acta neuropathologica》2010,120(2):131-143
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are usually associated with loss of dopaminergic neurons. Loss
of substantia nigra neurons and presence of Lewy body inclusions in some of the remaining neurons are the hallmark pathology
seen in the final stages of the disease. Attempts to correlate Lewy body pathology to either cell death or severity of clinical
symptoms, however, have not been successful. While the pathophysiology of the neurodegenerative process can hardly be explained
by Lewy bodies, the clinical symptoms do indicate a degenerative process located at the presynapse resulting in a neurotransmitter
deficiency. Recently it was shown that 90% or even more of α-synuclein aggregates in DLB cases were located at the presynapses
in the form of very small deposits. In parallel, dendritic spines are retracted, whereas the presynapses are relatively preserved,
suggesting a neurotransmitter deprivation. The same α-synuclein pathology can be demonstrated for PD. These findings give
rise to the notion that not cell death but rather α-synuclein aggregate-related synaptic dysfunction causes the neurodegeneration.
This opens new perspectives for understanding PD and DLB. If presynaptic α-synuclein aggregation, not neuronal loss, is the
key issue of the neurodegenerative process, then PD and DLB may eventually be treatable in the future. The disease may progress
via trans-synaptical spread, suggesting that stem cell transplants are of limited use. Future therapies may focus on the regeneration
of synapses. 相似文献
14.
Tetsuaki Arai Ian R. A. Mackenzie Masato Hasegawa Takashi Nonoka Kazhuhiro Niizato Kuniaki Tsuchiya Shuji Iritani Mitsumoto Onaya Haruhiko Akiyama 《Acta neuropathologica》2009,117(2):125-136
Phosphorylated and proteolytically cleaved TDP-43 is a major component of the ubiquitin-positive inclusions in the most common
pathological subtype of frontotemporal lobar degeneration (FTLD-U). Intracellular accumulation of TDP-43 is observed in a
subpopulation of patients with other dementia disorders, including Alzheimer’s disease (AD) and dementia with Lewy bodies
(DLB). However, the pathological significance of TDP-43 pathology in these disorders is unknown, since biochemical features
of the TDP-43 accumulated in AD and DLB brains, especially its phosphorylation sites and pattern of fragmentation, are still
unclear. To address these issues, we performed immunohistochemical and biochemical analyses of AD and DLB cases, using phosphorylation-dependent
anti-TDP-43 antibodies. We found a higher frequency of pathological TDP-43 in AD (36–56%) and in DLB (53–60%) than previously
reported. Of the TDP-43-positive cases, about 20–30% showed neocortical TDP-43 pathology resembling the FTLD-U subtype associated
with progranulin gene (PGRN) mutations. Immunoblot analyses of the sarkosyl-insoluble fraction from cases with neocortical TDP-43 pathology showed intense
staining of several low-molecular-weight bands, corresponding to C-terminal fragments of TDP-43. Interestingly, the band pattern
of these C-terminal fragments in AD and DLB also corresponds to that previously observed in the FTLD-U subtype associated
with PGRN mutations. These results suggest that the morphological and biochemical features of TDP-43 pathology are common between AD
or DLB and a specific subtype of FTLD-U. There may be genetic factors, such as mutations or genetic variants of PGRN underlying the co-occurrence of abnormal deposition of TDP-43, tau and α-synuclein. 相似文献
15.
TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer’s disease and frontotemporal lobar degeneration 总被引:2,自引:1,他引:1
Foulds P McAuley E Gibbons L Davidson Y Pickering-Brown SM Neary D Snowden JS Allsop D Mann DM 《Acta neuropathologica》2008,116(2):141-146
Autopsy studies have shown that about 55% of patients with frontotemporal lobar degeneration (FTLD) and 25% of patients with Alzheimer's disease (AD) harbour TDP-43 immunoreactive pathological changes in their brains. Using ELISA, we investigated whether we could detect the presence, or increased amounts, of TDP-43 in plasma of patients with FTLD and AD compared to normal control subjects. We detected elevated levels of TDP-43 protein in plasma of 46% patients with FTLD with clinical frontotemporal dementia (FTD) and 22% patients with AD, compared to 8% of control subjects. The proportions of patients with FTD and AD showing raised plasma TDP-43 levels correspond closely to those proportions known from autopsy studies to contain TDP-43 pathological changes in their brains. Raised TDP-43 plasma levels may thereby index TDP-43 pathology within the brain. Plasma TDP-43 levels may be a biomarker that can provide a laboratory test capable of identifying the presence of TDP-43 brain pathology in neurodegenerative disease during life. It may help to distinguish those cases of FTLD with ubiquitin/TDP-43 pathology in their brains from those with tauopathy. As a predictive test, plasma TDP-43 level may have great practical value in directing therapeutic strategies aimed at preventing or removing tau or TDP-43 pathological changes from the brain in FTLD and AD. 相似文献
16.
Newman J Rissman RA Sarsoza F Kim RC Dick M Bennett DA Cotman CW Rohn TT Head E 《Acta neuropathologica》2005,110(2):135-144
Alzheimers disease (AD), Picks disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or -synuclein. In AD, -amyloid (A)-associated caspase activation and cleavage of tau at Asp421 (Tau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether Tau accumulates in other diseases not characterized by extracellular A accumulation, we examined PiD, PSP, and CBD cases in comparison to those without extensive tau accumulation including frontotemporal lobar degeneration without Pick bodies (FTLD) and control cases. Additionally, we studied Tau accumulation in DLB cases associated with intracellular -synuclein. Tau was observed in all disease cases except non-PiD FTLD and controls. These results demonstrate that the accumulation of Tau may represent a common pathway associated with abnormal accumulation of intracellular tau or -synuclein and may be relatively less dependent on the extracellular accumulation of A in non-AD dementias. 相似文献
17.
Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy 总被引:4,自引:0,他引:4
Cerebral amyloid angiopathy (CAA) is defined by -amyloid peptide (A) depositions in cerebral vessels and is associated with Alzheimers disease (AD). The relationship between sporadic CAA and AD, and the origin of A in CAA are poorly understood. The aim of our study was to investigate the relationship between CAA and AD. Autopsy brains (n=113, 61.1% female, 55.8% clinically demented, age range 54–102 years, mean ± SE 83.5±0.93 years) underwent standardized neuropathological assessment. CAA was evaluated in frontal, frontobasal, hippocampal, and occipital regions. Using immunohistochemistry, the severity of A deposition in vessels was assessed semiquantitatively for each region separately. Evaluation of APOE genotype in 53 cases using real-time PCR showed significant correlations with severe AD pathology and CAA. CAA was present in 77 cases (68.1%), with the occipital region being affected significantly more often and more severely than other regions (P<0.01). Of brains without AD pathology 23.5% revealed CAA, whereas 24% with AD pathology showed no CAA. In concordance with other studies, the severity of both AD pathology and CAA showed a low, but significant correlation. This correlation, however, was only caused by the significant increase of occipital CAA with increasing AD pathology (P<0.01), and was independent of APOE genotype. Our results suggest that progressing AD pathology not only increases the severity of CAA, but also shifts its topographical distribution towards the occipital cortex. 相似文献
18.
Richard A. Armstrong Paul T. Kotzbauer Joel S. Perlmutter Meghan C. Campbell Kyle M. Hurth Robert E. Schmidt Nigel J. Cairns 《Journal of neural transmission (Vienna, Austria : 1996)》2014,121(2):171-181
The α-synuclein-immunoreactive pathology of dementia associated with Parkinson disease (DPD) comprises Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG). The densities of LB, LN, LG together with vacuoles, neurons, abnormally enlarged neurons (EN), and glial cell nuclei were measured in fifteen cases of DPD. Densities of LN and LG were up to 19 and 70 times those of LB, respectively, depending on region. Densities were significantly greater in amygdala, entorhinal cortex (EC), and sectors CA2/CA3 of the hippocampus, whereas middle frontal gyrus, sector CA1, and dentate gyrus were least affected. Low densities of vacuoles and EN were recorded in most regions. There were differences in the numerical density of neurons between regions, but no statistical difference between patients and controls. In the cortex, the density of LB and vacuoles was similar in upper and lower laminae, while the densities of LN and LG were greater in upper cortex. The densities of LB, LN, and LG were positively correlated. Principal components analysis suggested that DPD cases were heterogeneous with pathology primarily affecting either hippocampus or cortex. The data suggest in DPD: (1) ratio of LN and LG to LB varies between regions, (2) low densities of vacuoles and EN are present in most brain regions, (3) degeneration occurs across cortical laminae, upper laminae being particularly affected, (4) LB, LN and LG may represent degeneration of the same neurons, and (5) disease heterogeneity may result from variation in anatomical pathway affected by cell-to-cell transfer of α-synuclein. 相似文献
19.
Tanji K Mori F Kito K Kakita A Mimura J Itoh K Takahashi H Kamitani T Wakabayashi K 《Journal of neuropathology and experimental neurology》2011,70(10):879-889
α-Synuclein is a major component of Lewy bodies in Parkinson disease (PD) and dementia with Lewy bodies (DLB). We recently showed that abnormal α-synuclein with resistance to proteinase K (PK) is deposited at presynapses of distinct brain anatomic regions from the early stages of PD and DLB. NUB1, a synphilin-1-binding protein, also accumulates in Lewy bodies, but it is not known whether abnormal α-synuclein is associated with NUB1. Here, we demonstrate that, in the brain of patients with PD and DLB, NUB1 accumulates in the presynapses in the hippocampus, cerebral neocortex, and substantia nigra in which PK-resistant α-synuclein is deposited. Endogenous NUB1 also accumulated with PK-resistant α-synuclein in the presynapses of transgenic mice that express human α-synuclein with an A53T mutation. Immunoelectron microscopy showed that NUB1 is localized to presynaptic nerve terminals where no abnormal filaments are seen. Biochemical analyses showed that NUB1 coexists with abnormal α-synuclein in the brain of DLB patients. These findings suggest that NUB1 along with abnormal α-synuclein is involved in the pathogenesis of Lewy body disease. 相似文献
20.
Laske C Fallgatter AJ Stransky E Hagen K Berg D Maetzler W 《Dementia and geriatric cognitive disorders》2011,31(6):413-416
Background/Aims: Detection and differentiation of neurodegenerative dementias, such as dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), with blood-based biomarkers would facilitate diagnosis and treatment. Methods: By use of a commercially available ELISA kit, we measured α-synuclein levels in the serum of 40 DLB patients and controls, and of 80 AD patients. Results: We found significantly reduced α-synuclein serum levels in DLB compared to both AD (p = 0.006) and control subjects (p = 0.001), reaching an area under the curve of >0.70. Conclusion: Although these results do not justify a definition of serum α-synuclein as a potential single biomarker, results may contribute to a multimarker strategy in DLB diagnosis. 相似文献