scholarly journals Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Karlijn J. Doorn ◽  
Benjamin Drukarch ◽  
Anne-Marie van Dam ◽  
Paul J. Lucassen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subventricular Zone ◽  
Lewy Body Disease ◽  
Minichromosome Maintenance ◽  
Proliferating Cells ◽  
Cognitive Changes ◽  
Incidental Lewy Body Disease ◽  
Minichromosome Maintenance Protein ◽  
Microglial Response

Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to accumulation ofα-synuclein in the hippocampus (HC). This brain region also contains stem cells that can proliferate. This is a well-regulated process that can, for example, be altered by neurodegenerative conditions. In contrast to proliferation in the substantia nigra and subventricular zone, little is known about the HC in PD. In addition, glial cells contribute to neurodegenerative processes and may proliferate in response to PD pathology. In the present study, we questioned whether microglial cells proliferate in the HC of established PD patients versus control subjects or incidental Lewy body disease (iLBD) cases as a prodromal state of PD. To this end, proliferation was assessed using the immunocytochemical marker minichromosome maintenance protein 2 (MCM2). Colocalization with Iba1 was performed to determine microglial proliferation. MCM2-positive cells were present in the HC of controls and were significantly increased in the presymptomatic iLBD cases, but not in established PD patients. Microglia represented the majority of the proliferating cells in the HC. This suggests an early microglial response to developing PD pathology in the HC and further indicates that neuroinflammatory processes play an important role in the development of PD pathology.

scholarly journals Olfactory dysfunction in incidental Lewy body disease and Parkinson's disease

2014 ◽  
Vol 20 (11) ◽  
pp. 1260-1262 ◽  
Author(s):  
Erika Driver-Dunckley ◽  
Charles H. Adler ◽  
Joseph G. Hentz ◽  
Brittany N. Dugger ◽  
Holly A. Shill ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Olfactory Dysfunction ◽  
Incidental Lewy Body Disease

scholarly journals Evidence for angiogenesis in Parkinson’s disease, incidental Lewy body disease, and progressive supranuclear palsy

2011 ◽  
Vol 119 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Brinda Desai Bradaric ◽  
Aditiben Patel ◽  
Julie A. Schneider ◽  
Paul M. Carvey ◽  
Bill Hendey
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Progressive Supranuclear Palsy ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Incidental Lewy Body Disease

Vagus Nerve and Stomach Synucleinopathy in Parkinson’s Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the “Body-First” Hypothesis

2021 ◽  
pp. 1-11
Author(s):  
Thomas G. Beach ◽  
Charles H. Adler ◽  
Lucia I. Sue ◽  
Holly A. Shill ◽  
Erika Driver-Dunckley ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Vagus Nerve ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Normal Subjects ◽  
The Body ◽  
Gastric Body ◽  
Elderly Subjects ◽  
Incidental Lewy Body Disease

Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. Objective: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. Methods: Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. Results: Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. Conclusion: As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.

scholarly journals Alterations in peptide levels in Parkinson's disease and incidental Lewy body disease

Brain ◽  
1996 ◽  
Vol 119 (3) ◽  
pp. 823-830 ◽  
Author(s):  
A. Fernandez ◽  
M. L. de Ceballos ◽  
S. Rose ◽  
P. Jenner ◽  
C. D. Marsden
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Incidental Lewy Body Disease

scholarly journals Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson’s Disease

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 139
Author(s):  
Alexis Fenyi ◽  
Charles Duyckaerts ◽  
Luc Bousset ◽  
Heiko Braak ◽  
Kelly Del Tredici ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Fixed Tissue ◽  
Incidental Lewy Body Disease ◽  
Seeding Efficiency ◽  
Formalin Fixed

We investigated α-synuclein’s (αSyn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic αSyn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson’s disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant αSyn assemblies were determined by limited proteolysis and transmission electron microscopy. We show that fixed tissue from Parkinson’s disease (PD) and incidental Lewy body disease (ILBD) seeds the aggregation of monomeric αSyn into fibrillar assemblies. Significant variations in the characteristics of fibrillar assemblies derived from different regions even within the same individual were observed. This finding suggests that fixation stabilizes seeds with an otherwise limited seeding propensity, that yield assemblies with different intrinsic structures (i.e., strains). The lag phase preceding fibril assembly for patients ≥80 was significantly shorter than in other age groups, suggesting the existence of increased numbers of seeds or a higher seeding potential of pathogenic αSyn with time. Seeding activity did not diminish in late-stage disease. No statistically significant difference in the seeding efficiency of specific regions was found, nor was there a relationship between seeding efficiency and the load of pathogenic αSyn in a particular region at a given neuropathological stage.

scholarly journals Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients

2021 ◽  
Vol 14 ◽  
Author(s):  
Katarína Tiklová ◽  
Linda Gillberg ◽  
Nikolaos Volakakis ◽  
Hilda Lundén-Miguel ◽  
Lina Dahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Lewy Body Disease ◽  
Dopamine Neurons ◽  
Differentially Expressed ◽  
Incidental Lewy Body Disease ◽  
Advanced Stages ◽  
Midbrain Dopamine

Analyses of gene expression in cells affected by neurodegenerative disease can provide important insights into disease mechanisms and relevant stress response pathways. Major symptoms in Parkinson’s disease (PD) are caused by the degeneration of midbrain dopamine (mDA) neurons within the substantia nigra. Here we isolated neuromelanin-positive dopamine neurons by laser capture microdissection from post-mortem human substantia nigra samples recovered at both early and advanced stages of PD. Neuromelanin-positive cells were also isolated from individuals with incidental Lewy body disease (ILBD) and from aged-matched controls. Isolated mDA neurons were subjected to genome-wide gene expression analysis by mRNA sequencing. The analysis identified hundreds of dysregulated genes in PD. Results showed that mostly non-overlapping genes were differentially expressed in ILBD, subjects who were early after diagnosis (less than five years) and those autopsied at more advanced stages of disease (over five years since diagnosis). The identity of differentially expressed genes suggested that more resilient, stably surviving DA neurons were enriched in samples from advanced stages of disease, either as a consequence of positive selection of a less vulnerable long-term surviving mDA neuron subtype or due to up-regulation of neuroprotective gene products.

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