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Hallmark Lesions (hallmark + lesion)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Pathological biochemistry of ,-synucleinopathy

NEUROPATHOLOGY, Issue 5 2007
Takeshi Iwatsubo
Lewy bodies (LBs) are hallmark lesions in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We raised a monoclonal antibody LB509 against purified LBs from the brains of patients with DLB that strongly immuolabled LBs, and found that ,-synuclein is one of the major components of LBs. Thus, the deposition of ,-synuclein, an abundant presynaptic brain protein, as fibrillary aggregates in affected neurons or glial cells, was highlighted as a hallmark lesion of a subset of neurodegenerative disorders, including PD, DLB and multiple system atrophy collectively referred to as synucleinopathies. Importantly, the identification of missense mutations in and multiplication of ,-synuclein gene in some pedigrees of familial PD has strongly implicated ,-synuclein in the pathogenesis of PD and other synucleinopathies. We then examined the specific post-translational modifications that characterize and underlie the aggregation of ,-synuclein in synucleinopathy brains by mass spectrometry and using a specific antibody, and found that serine 129 of ,-synuclein deposited in synucleinopathy lesions is selectively and extensively phosphorylated. Furthermore we generated transgenic C. elegans overexpressing ,-synuclein in neurons, and found that overexpression of familial PD-linked mutant form of ,-synuclein impairs functions of dopamine neurons. These findings collectively underscore the importance of deposition of ,-synuclein as well as its phosphorylation in the pathogenesis of ,-synucleinopathies. [source]

Olfactory pathogenesis of idiopathic Parkinson disease revisited

MOVEMENT DISORDERS, Issue 8 2008
Alicja Lerner MD
Abstract Idiopathic Parkinson disease (PD) is traditionally considered a movement disorder with hallmark lesions located in the substantia nigra pars compacta (SNpc). However, recent histopathological studies of some PD cases suggest the possibility of a multisystem disorder which progresses in a predictable sequence as described in Braak's staging criteria. The disease process starts in the dorsal motor nucleus of the vagus (dmX) and anterior olfactory nucleus and bulb, and from there, spreads through the brainstem nuclei to ultimately reach the SNpc, which then presents as symptomatic PD. In this article, we would like to revisit the olfactory pathogenesis of PD based on Braak's staging system and review anatomical pathways supporting such a possibility. We also suggest some biomarkers for early stages of PD. Additionally, we present and discuss the possibility that a prion-like process underlies the neurodegenerative changes in PD. © 2008 Movement Disorder Society [source]

Pathological biochemistry of ,-synucleinopathy

NEUROPATHOLOGY, Issue 5 2007
Takeshi Iwatsubo
Lewy bodies (LBs) are hallmark lesions in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We raised a monoclonal antibody LB509 against purified LBs from the brains of patients with DLB that strongly immuolabled LBs, and found that ,-synuclein is one of the major components of LBs. Thus, the deposition of ,-synuclein, an abundant presynaptic brain protein, as fibrillary aggregates in affected neurons or glial cells, was highlighted as a hallmark lesion of a subset of neurodegenerative disorders, including PD, DLB and multiple system atrophy collectively referred to as synucleinopathies. Importantly, the identification of missense mutations in and multiplication of ,-synuclein gene in some pedigrees of familial PD has strongly implicated ,-synuclein in the pathogenesis of PD and other synucleinopathies. We then examined the specific post-translational modifications that characterize and underlie the aggregation of ,-synuclein in synucleinopathy brains by mass spectrometry and using a specific antibody, and found that serine 129 of ,-synuclein deposited in synucleinopathy lesions is selectively and extensively phosphorylated. Furthermore we generated transgenic C. elegans overexpressing ,-synuclein in neurons, and found that overexpression of familial PD-linked mutant form of ,-synuclein impairs functions of dopamine neurons. These findings collectively underscore the importance of deposition of ,-synuclein as well as its phosphorylation in the pathogenesis of ,-synucleinopathies. [source]

Severe Vascular Lesions and Poor Functional Outcome in Kidney Transplant Recipients with Lupus Anticoagulant Antibodies

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010
G. Canaud
The impact of antiphospholipid antibodies (APA) on clinical outcome and graft histology following renal transplantation remains poorly known and controversial. We retrospectively explored the functional and histological significance of APA, primarily lupus anticoagulant (LA), in kidney transplant recipients using a systematic evaluation of 3- and 12-month posttransplant screening biopsies and glomerular filtration rate measurements (mGFR). During the study period, 37 patients had APA (2.7%), primarily LA, and 12 fulfiled antiphospholipid syndrome (APS) diagnostic criteria (0.8%) at the time of transplantation. Early after transplantion, 4 of the 12 APS patients died. Early thrombosis of graft vessels and deep venous thrombosis occurred more frequently in APA+ patients than in controls (27% vs. 7%, p < 0.05 and 35% vs. 14%, p < 0.05, respectively). The survival rate was significantly lower in patients with APS. Strikingly, the hallmark lesions of APS-associated nephropathy (APSN) were found in most of screening graft biopsies in APA+ patients but not in the controls. Accordingly, APA+ patients had a dramatic increase in chronic vascular scores and a faster decline in mGFR at 1 year. In conclusion, renal transplantation may be life-threatening in APS patients, and the presence of LA at the time of transplantation is associated with a high rate of allograft APSN and poor transplantation outcomes. [source]