Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain sp...Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood-brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.展开更多
Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with ...Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.展开更多
Tremor is the most common movement disorder characterized by a rhythmical,involuntary oscillatory movement of a body part.Since distinct diseases can cause similar tremor manifestations and vice-versa,it is challengin...Tremor is the most common movement disorder characterized by a rhythmical,involuntary oscillatory movement of a body part.Since distinct diseases can cause similar tremor manifestations and vice-versa,it is challenging tomake an accurate diagnosis.This applies particularly for tremor at rest.This entity was only rarely studied in the past,although a multitude of clinical studies on prevalence and clinical features of tremor in Parkinson’s disease(PD),essential tremor and dystonia,have been carried out.Monosymptomatic rest tremor has been further separated from tremor-dominated PD.Rest tremor is also found in dystonic tremor,essential tremor with a rest component,Holmes tremor and a few even rarer conditions.Dopamine transporter imaging and several electrophysiological methods provide additional clues for tremor differential diagnosis.New evidence from neuroimaging and electrophysiological studies has broadened our knowledge on the pathophysiology of Parkinsonian and non-Parkinsonian tremor.Large cohort studies are warranted in future to explore the nature course and biological basis of tremor in common tremor related disorders.展开更多
文摘Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood-brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.
基金Intramural funding of the Dept.of Neurology,Kiel University.
文摘Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.
基金Wei Chen received grants from Youth Fund of Shanghai Ninth People’s Hospital,K.C.Wong Medical Fund of Shanghai Jiao Tong University,and National Natural Science Fund of China(81401039).
文摘Tremor is the most common movement disorder characterized by a rhythmical,involuntary oscillatory movement of a body part.Since distinct diseases can cause similar tremor manifestations and vice-versa,it is challenging tomake an accurate diagnosis.This applies particularly for tremor at rest.This entity was only rarely studied in the past,although a multitude of clinical studies on prevalence and clinical features of tremor in Parkinson’s disease(PD),essential tremor and dystonia,have been carried out.Monosymptomatic rest tremor has been further separated from tremor-dominated PD.Rest tremor is also found in dystonic tremor,essential tremor with a rest component,Holmes tremor and a few even rarer conditions.Dopamine transporter imaging and several electrophysiological methods provide additional clues for tremor differential diagnosis.New evidence from neuroimaging and electrophysiological studies has broadened our knowledge on the pathophysiology of Parkinsonian and non-Parkinsonian tremor.Large cohort studies are warranted in future to explore the nature course and biological basis of tremor in common tremor related disorders.
