scholarly journals What Do Israeli Gerontology Students Think About Medical Marijuana Use for Alzheimer’s and Parkinson’s Disease?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 351-351
Author(s):  
Offer Edelstein ◽  
Richard Isralowitz ◽  
Oren Wacht ◽  
Alexander Reznik ◽  
Yaacov Bachner
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Graduate Students ◽  
Online Survey ◽  
Formal Education ◽  
Service Providers ◽  
Marijuana Use ◽  
Positive Attitudes ◽  
Age Related ◽  
Recreational Marijuana

Abstract Aims The aims of the current study were as follows: 1) to assess gerontology graduate students’ beliefs about medical marijuana’s (MMJ) effectiveness for two common age-related conditions - Alzheimer’s (AD) and Parkinson’s disease (PD); 2) to assess students’ beliefs and attitudes toward MMJ; 3) to explore associations linking background characteristics, MMJ-related attitudes and beliefs, and beliefs about the MMJ effectiveness for AD and PD. Method A sample of 104 (84 women and 20 men) gerontology graduate students voluntarily participated in an anonymous online survey. Results The vast majority (95%) of the participants indicated they had no formal education about MMJ and reported being unprepared to answer clients’ MMJ-related questions (84.6%). Most of the participants believed that MMJ is effective for use with AD (70.2%) and PD (80.8%) patients. Participants reported favorable beliefs about MMJ benefits, concerns about risks, the need for training, and positive attitudes toward recreational marijuana use legalization. Prior marijuana use (e.g., self-use, friends or family) was found to be associated with more positive beliefs about MMJ benefits, risks, and its legalization for recreational purposes. Prior marijuana use was the only factor associated with the belief that MMJ is an effective therapy for use with individuals diagnosed with AD or PD. Conclusions The study findings stress the need for students’ MMJ education in order to provide future gerontology service providers with the necessary knowledge and ability to address clients’ questions about MMJ use. Efforts to develop curricula and training programs need to be promoted.

scholarly journals The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Symptom Onset ◽  
Disease Risk ◽  
Age Of Onset ◽  
Sequencing Analysis ◽  
Age Related ◽  
Australian Cohort ◽  
Progression Markers ◽  
Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

scholarly journals Sex- and age‐dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kelly B. Menees ◽  
Rachael H. Earls ◽  
Jaegwon Chung ◽  
Janna Jernigan ◽  
Nikolay M. Filipov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sex Differences ◽  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Spleen Weight ◽  
Age Related ◽  
And Function ◽  
Cell Phenotypes

Abstract Background Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood. Results Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis. Conclusions This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.

Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson’s Disease Is Modified by the SNCA rs356181 Polymorphism

2018 ◽  
Vol 18 (5-6) ◽  
pp. 233-238
Author(s):  
Frederic Sampedro ◽  
Juan Marín-Lahoz ◽  
Saul Martínez-Horta ◽  
Javier Pagonabarraga ◽  
Jaime Kulisevsky
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
De Novo ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Csf Biomarkers ◽  
Gene Encoding ◽  
Cortical Thinning ◽  
Age Related

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson’s disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson’s Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP’s genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.

scholarly journals Age-related pathological impairments in induced neurons derived from patients with idiopathic Parkinson’s disease

2021 ◽  
Author(s):  
Janelle Drouin-Ouellet ◽  
Karolina Pircs ◽  
Emilie M. Legault ◽  
Marcella Birtele ◽  
Fredrik Nilsson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alpha Synuclein ◽  
Specific Model ◽  
Dermal Fibroblasts ◽  
Patient Specific ◽  
Idiopathic Parkinson’S Disease ◽  
Age Related ◽  
Idiopathic Parkinson's Disease ◽  
Induced Neurons

AbstractUnderstanding the pathophysiology of Parkinson’s disease has been hampered by the lack of models that recapitulate all the critical factors underlying its development. Here, we generated functional induced dopaminergic neurons (iDANs) that were directly reprogrammed from adult human dermal fibroblasts of patients with idiopathic Parkinson’s disease to investigate diseaserelevant pathology. We show that iDANs derived from Parkinson’s disease patients exhibit lower basal chaperone-mediated autophagy as compared to iDANs of healthy donors. Furthermore, stress-induced autophagy resulted in an accumulation of macroautophagic structures in induced neurons (iNs) derived from Parkinson’s disease patients, independently of the specific neuronal subtype but dependent on the age of the donor. Finally, we found that these impairments in patient-derived iNs lead to an accumulation of phosphorylated alpha-synuclein, a hallmark of Parkinson’s disease pathology. Taken together, our results demonstrate that direct neural reprogramming provides a patient-specific model to study aged neuronal features relevant to idiopathic Parkinson’s disease.

scholarly journals Severe and regionally-widespread increases in tissue urea in the human brain represent a novel finding of pathogenic potential in Parkinson’s disease dementia

2021 ◽  
Author(s):  
Melissa Scholefield ◽  
Stephanie J. Church ◽  
Jingshu Xu ◽  
Stefano Patassini ◽  
Federico Roncaroli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Performance ◽  
Current Knowledge ◽  
Neuronal Loss ◽  
Middle Temporal Gyrus ◽  
Parkinson’S Disease Dementia ◽  
Pathogenic Potential ◽  
Age Related ◽  
Liquid Chromatography Tandem Mass

Abstract Background: Widespread elevations in brain urea have, in recent years, been reported in certain types of age-related dementia, notably Alzheimer’s disease (AD) and Huntington’s disease (HD). Urea increases in these diseases are substantive, and approximate in magnitude to levels present in uraemic encephalopathy. In AD and HD, elevated urea levels occur across the entire brain, and not only in regions heavily affected by neurodegeneration. However, measurements of brain urea have not hitherto been reported in Parkinson’s disease dementia (PDD), a condition defined by changes in thinking and behaviour in someone with a diagnosis of Parkinson's disease, which shares neuropathological and symptomatic overlap with both AD and HD. This study aims to address this gap in the current knowledge of PDD.Methods: Here we report measurements of tissue urea from nine neuropathologically-confirmed regions of the brain in PDD and post-mortem-delay-matched controls, in regions that included the cerebellum, motor cortex, sensory cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons, by applying ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Case-control differences were determined using multiple t-tests followed by correction with 10% false discovery rate.Results: We found urea concentrations to be substantively elevated in all nine regions, the average increase being 3-4-fold. Urea concentrations were remarkably consistent across regions in both cases and controls, with no clear distinction between regions heavily affected by neuronal loss in PDD compared to less severely affected areas. These urea elevations mirror those found in uraemic encephalopathy, where equivalent levels are generally considered to be pathogenic. These urea elevations also reflect those previously reported in AD and HD. Conclusions: Increased urea is a widespread metabolic perturbation in brain metabolism common to PDD, AD, and HD, at levels equal to those seen in uremic encephalopathy. This presents a novel pathogenic mechanism in PDD, which is shared with two other neurodegenerative diseases.

scholarly journals Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Epaminondas Doxakis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Clinical Manifestations ◽  
Alpha Synuclein ◽  
Circular Rnas ◽  
Age Related ◽  
And Function ◽  
The Brain

AbstractParkinson’s disease (PD) is a complex, age-related, neurodegenerative disease whose etiology, pathology, and clinical manifestations remain incompletely understood. As a result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are a large class of mostly noncoding RNAs that accumulate with aging in the brain and are increasingly shown to regulate all aspects of neuronal and glial development and function. They are generated by the spliceosome through the backsplicing of linear RNA. Although their biological role remains largely unknown, they have been shown to regulate transcription and splicing, act as decoys for microRNAs and RNA binding proteins, used as templates for translation, and serve as scaffolding platforms for signaling components. Considering that they are stable, diverse, and detectable in easily accessible biofluids, they are deemed promising biomarkers for diagnosing diseases. CircRNAs are differentially expressed in the brain of patients with PD, and growing evidence suggests that they regulate PD pathogenetic processes. Here, the biogenesis, expression, degradation, and detection of circRNAs, as well as their proposed functions, are reviewed. Thereafter, research linking circRNAs to PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, and oxidative stress is highlighted, followed by recent evidence for their use as prognostic and diagnostic biomarkers for PD.

scholarly journals Strain- and age-dependent features of the nigro-striatal circuit in three common laboratory mouse strains, C57BL/6J, A/J, and DBA/2J - Implications for Parkinson’s disease modeling

2020 ◽  
Author(s):  
Mélanie H. Thomas ◽  
Mona Karout ◽  
Beatriz Pardo Rodriguez ◽  
Yujuan Gui ◽  
Christian Jaeger ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Brain ◽  
Dopaminergic Neurons ◽  
Mouse Strains ◽  
List Type ◽  
Background Strain ◽  
Age Related ◽  
Health And Disease ◽  
Over Time

AbstractMouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.HighlightsStudy of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different agesAge related evolution of essential features of nigral dopaminergic neurons differ between strainsConsider background strain and age is crutial to study the nigrostriatal circuit in health and disease

scholarly journals Elevated HDL Levels Linked to Poorer Cognitive Ability in Females With Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Megan C. Bakeberg ◽  
Anastazja M. Gorecki ◽  
Jade E. Kenna ◽  
Alexa Jefferson ◽  
Michelle Byrnes ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Cognitive Performance ◽  
Linear Models ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cognitive Status ◽  
Cross Sectional ◽  
Age Related

IntroductionCholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson’s disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients.MethodsCognitive function was evaluated using two validated assessments (ACE-R and SCOPA-COG) in 182 people with PD from the Australian Parkinson’s Disease Registry. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Triglyceride (TRG) levels were examined within this cohort. The influence of individual lipid subfractions on domain-specific cognitive performance was investigated using covariate-adjusted generalised linear models.ResultsFemales with PD exhibited significantly higher lipid subfraction levels (TC, HDL, and LDL) when compared to male counterparts. While accounting for covariates, HDL levels were strongly associated with poorer performance across multiple cognitive domains in females but not males. Conversely, TC and LDL levels were not associated with cognitive status in people with PD.ConclusionHigher serum HDL associates with poorer cognitive function in females with PD and presents a sex-specific biomarker for cognitive impairment in PD.

scholarly journals Multiple genetic pathways regulating lifespan extension are neuroprotective in a G2019S LRRK2 nematode model of Parkinson’s disease

2020 ◽  
Author(s):  
Megan M. Senchuk ◽  
Jeremy M. Van Raamsdonk ◽  
Darren J. Moore
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Lifespan Extension ◽  
Disease Manifestation ◽  
Genetic Pathways ◽  
Dopaminergic Neurodegeneration ◽  
Age Related ◽  
Increased Risk ◽  
Extended Longevity

AbstractBackgroundMutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of late-onset, familial Parkinson’s disease (PD), and LRRK2 variants are associated with increased risk for sporadic PD. While advanced age represents the strongest risk factor for disease development, it remains unclear how different age-related pathways interact to regulate LRRK2-driven late-onset PD.FindingsIn this study, we employ a C.elegans model expressing PD-linked G2019S LRRK2 to examine the interplay between age-related pathways and LRRK2-induced dopaminergic neurodegeneration. We find that multiple genetic pathways that regulate lifespan extension can provide robust neuroprotection against mutant LRRK2. However, the level of neuroprotection does not strictly correlate with the magnitude of lifespan extension, suggesting that lifespan can be experimentally dissociated from neuroprotection. Using tissue-specific RNAi, we demonstrate that lifespan-regulating pathways, including insulin/IGF-1 signaling, TOR, and mitochondrial respiration, can be directly manipulated in neurons to mediate neuroprotection. We extend this finding for AGE-1/PI3K, where pan-neuronal versus dopaminergic neuronal restoration of AGE-1 reveals both cell-autonomous and non-cell-autonomous neuroprotective mechanisms downstream of insulin signaling.ConclusionsOur data demonstrate the importance of distinct lifespan-regulating pathways in the pathogenesis of LRRK2-linked PD, and suggest that extended longevity is broadly neuroprotective via the actions of these pathways at least in part within neurons. This study further highlights the complex interplay that occurs between cells and tissues during organismal aging and disease manifestation.

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