scholarly journals Clinical Manifestations of Parkinson's Disease and Parkinsonism

Author(s):  
Doug Everett Hobson

The most common disorder in a patient presenting to a movement disorder clinic will be parkinsonism. The challenge is to provide the patient with the most accurate diagnosis and prognosis possible. The assumption at the time of initial presentation of the clinical diagnosis of Parkinson's disease is often wrong (20-25%). Waiting to see the pattern of progression, and response to medication provides invaluable additional information. This manuscript summarizes the clinical manifestations of Parkinson's disease and the main akinetic-rigid syndromes (progressive supranuclear palsy, multiple system atrophy, cortical-basal ganglionic degeneration, and dementia with Lewy bodies) that make up the differential diagnosis.

Author(s):  
Manuel Schweighauser ◽  
Yang Shi ◽  
Airi Tarutani ◽  
Fuyuki Kametani ◽  
Alexey G. Murzin ◽  
...  

Synucleinopathies are human neurodegenerative diseases that include multiple system atrophy (MSA), Parkinson’s disease, Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) (1). Existing treatments are at best symptomatic. These diseases are characterised by the presence in brain cells of filamentous inclusions of α-synuclein, the formation of which is believed to cause disease (2, 3). However, the structures of α-synuclein filaments from human brain are not known. Here we show, using electron cryo-microscopy, that α-synuclein inclusions from MSA are made of two types of filaments, each of which consists of two different protofilaments. Non-proteinaceous molecules are present at the protofilament interfaces. By two-dimensional class averaging, we show that α-synuclein filaments from the brains of patients with MSA and DLB are different, suggesting that distinct conformers (or strains) characterise synucleinopathies. As was the case of tau assemblies (4–9), the structures of α-synuclein filaments extracted from the brains of individuals with MSA differ from those formed in vitro using recombinant proteins, with implications for understanding the mechanisms of aggregate propagation and neurodegeneration in human brain. These findings have diagnostic and potential therapeutic relevance, especially in view of the unmet clinical need to be able to image filamentous α-synuclein inclusions in human brain.


1998 ◽  
Vol 251 (3) ◽  
pp. 205-208 ◽  
Author(s):  
Maria Grazia Spillantini ◽  
R. Anthony Crowther ◽  
Ross Jakes ◽  
Nigel J. Cairns ◽  
Peter L. Lantos ◽  
...  

Author(s):  
Isabelle Lavenir ◽  
Daniela Passarella ◽  
Masami Masuda-Suzukake ◽  
Annabelle Curry ◽  
Janice L. Holton ◽  
...  

Abstract Synucleinopathies [Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA)] share filamentous α-synuclein assemblies in nerve cells and glial cells. We compared the abilities of brain extracts from MSA and PD patients to induce neuronal α-synuclein assembly and neurodegeneration following intracerebral injection in heterozygous mice transgenic for human mutant A53T α-synuclein. MSA extracts were more potent than PD extracts in inducing α-synuclein assembly and in causing neurodegeneration. MSA assemblies were Campbell-Switzer- and Gallyas-silver-positive, whereas PD assemblies were only Campbell-Switzer-positive, in confirmation of previous findings. However, induced α-synuclein inclusions were invariably Campbell-Switzer-positive and Gallyas-negative, irrespective of whether MSA or PD brain extracts were injected. The α-synuclein inclusions of non-injected homozygous mice transgenic for A53T α-synuclein were also Campbell-Switzer-positive and Gallyas-negative. These findings demonstrate that transgene expression and its intracellular environment dominated over the silver staining properties of the conformers of assembled α-synuclein.


Sign in / Sign up

Export Citation Format

Share Document