Journal of Parkinson's disease and Alzheimer's disease最新文献

{"title":"Development of AD-Like Pathology in Skeletal Muscle.","authors":"X Chen, N M Miller, Z Afghah, J D Geiger","doi":"10.13188/2376-922x.1000028","DOIUrl":"10.13188/2376-922x.1000028","url":null,"abstract":"<p><p>Effective therapeutic strategy against Alzheimer's disease (AD) requires early detection of AD; however, clinical diagnosis of Alzheimer's disease (AD) is not precise and a definitive diagnosis of AD is only possible via postmortem examination for AD pathological hallmarks including senile plaques composed of Aβ and neuro fibrillary tangles composed of phosphorylated tau. Although a variety of biomarker has been developed and used in clinical setting, none of them robustly predicts subsequent clinical course of AD. Thus, it is essential to identify new biomarkers that may facilitate the diagnosis of early stages of AD, prediction of subsequent clinical course, and development of new therapeutic strategies. Given that pathological hallmarks of AD including Aβaccumulation and the presence of phosphorylated tau are also detected in peripheral tissues, AD is considered a systemic disease. Without the protection of blood-brain barrier, systemic factors can affect peripheral tissues much earlier than neurons in brain. Here, we will discuss the development of AD-like pathology in skeletal muscle and the potential use of skeletal muscle biopsy (examination for Aβaccumulation and phosphorylated tau) as a biomarker for AD.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079679/pdf/nihms-1042472.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37752598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Advantages of Dual Targeting of PPAR-δ and PPAR-γ in an Experimental Model of Sporadic Alzheimer's Disease.","authors":"D Reich,&nbsp;G Gallucci,&nbsp;M Tong,&nbsp;S M de la Monte","doi":"10.13188/2376-922X.1000025","DOIUrl":"https://doi.org/10.13188/2376-922X.1000025","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is associated with progressive impairments in brain responsiveness to insulin and insulin-like growth factor (IGF). Although deficiencies in brain insulin and IGF could be ameliorated with trophic factors such as insulin, impairments in receptor expression, binding, and tyrosine kinase activation require alternative strategies. Peroxisome proliferator-activated receptor (PPAR) agonists target genes downstream of insulin/IGF stimulation. Furthermore, their anti-oxidant and anti-inflammatory effects address other pathologies contributing to neurodegeneration.</p><p><strong>Objectives: </strong>The goal of this research was to examine effects of dual delivery of L165, 041 (PPAR-δ) and F-L-Leu (PPAR-γ) agonists for remediating in the early stages of neurodegeneration.</p><p><strong>Model: </strong>Experiments were conducted using frontal lobe slice cultures from an intracerebral Streptozotocin (i.c. STZ) rat model of AD.</p><p><strong>Results: </strong>PPAR-δ+ PPAR-γ agonist treatments increased indices of neuronal and myelin maturation, and mitochondrial proliferation and function, and decreased neuroinflammation, AβPP-Aβ, neurotoxicity, ubiquitin, and nitrosative stress, but failed to restore choline acetyl transferase expression and adversely increased HNE(lipid peroxidation) and acetylcholinesterase, which would have further increased stress and reduced cholinergic function in the STZ brain cultures.</p><p><strong>Conclusion: </strong>PPAR-δ + PPAR-γ agonist treatments have substantial positive early therapeutic targeting effects on AD-associated molecular and biochemical brain pathologies. However, additional or alternative strategies may be needed to optimize disease remediation during the initial phases of treatment.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36918859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Non-Pharmacological Treatments on Quality of Life in Parkinson's Disease: A Review.","authors":"Sangwoo Ahn,&nbsp;Yan Chen,&nbsp;Tim Bredow,&nbsp;Corjena Cheung,&nbsp;Fang Yu","doi":"10.13188/2376-922X.1000021","DOIUrl":"https://doi.org/10.13188/2376-922X.1000021","url":null,"abstract":"<p><p>Parkinson's disease is a neurodegenerative chronic condition with a declining trajectory and lack of a cure, making quality of life an important aspect of care. The purpose of this literature review was to analyze the state-of-the-science on the effects of non-pharmacological treatments on quality of life in person's with Parkinson's disease. Literature search was conducted using keywords in electronic databases up to September 1, 2016 and cross-searching the references of identified articles. Of the 259 articles generated, 26 met the eligibility criteria and were included in this review. The majority of studies (77%) were Level I evidence and 23% Level II evidence. The levels of study quality were: strong (50%), moderate (15%), and weak (35%). The interventions varied across studies with 15 studies evaluating a similar intervention. About 58% of the studies showed that the interventions improved quality of life. In conclusion, a variety of non-pharmacological interventions have been increasingly studied for their effects on quality of life in Parkinson's disease, showing initial promising results. However, most interventions were only examined by a limited number of studies and the minimal and optimal intervention doses needed for improving quality of life are yet unknown.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602569/pdf/nihms871406.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35532166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons from a Rare Familial Dementia: Amyloid and Beyond.","authors":"Adam Cantlon,&nbsp;Carlo Sala Frigerio,&nbsp;Dominic M Walsh","doi":"10.13188/2376-922X.1000009","DOIUrl":"https://doi.org/10.13188/2376-922X.1000009","url":null,"abstract":"<p><p>Here we review the similarities between a rare inherited disorder, familial British dementia (FBD), and the most common of all late-life neurological conditions, Alzheimer's diseases (AD). We describe the symptoms, pathology and genetics of FBD, the biology of the BRI2 protein and mouse models of FBD and familial Danish dementia. In particular, we focus on the evolving recognition of the importance of protein oligomers and aberrant processing of the amyloid β-protein precursor (APP) - themes that are common to both FBD and AD. The initial discovery that FBD is phenotypically similar to AD, but associated with the deposition of an amyloid peptide (ABri) distinct from the amyloid β-protein (Aβ) led many to assume that amyloid production alone is sufficient to initiate disease and that ABri is the molecular equivalent of Aβ. Parallel with work on Aβ, studies of ABri producing animal models and in vitro ABri toxicity experiments caused a revision of the amyloid hypothesis and a focus on soluble oligomers of Aβ and ABri. Contemporaneous other studies suggested that loss of the ABri precursor protein (BRI2) may underlie the cognitive deficits in FBD. In this regard it is important to note that BRI2 has been shown to interact with and regulate the processing of APP, and that mutant BRI2 leads to altered cleavage of APP. A synthesis of these results suggests that a \"two-hit mechanism\" better explains FBD than earlier toxic gain of function and toxic loss of function models. The lessons learned from the study of FBD imply that the molecular pathology of AD is also likely to involve both aberrant aggregation (in AD, Aβ) and altered APP processing. With regard to FBD, we propose that the C-terminal 11 amino acid of FBD-BRI2 interfere with both the normal function of BRI2 and promotes the production of cystine cross-linked toxic ABri oligomers. In this scenario, loss of BRI2 function leads to altered APP processing in as yet underappreciated ways. Given the similarities between FBD and AD it seems likely that study of the structure of ABri oligomers and FBD-induced changes in APP metabolites will further our understanding of AD.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34102475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative Splicing in Alzheimer’s Disease","authors":"Julia E Love, Eric J. Hayden, T. Rohn","doi":"10.13188/2376-922X.1000010","DOIUrl":"https://doi.org/10.13188/2376-922X.1000010","url":null,"abstract":"Neurodegenerative diseases have a variety of different genes contributing to their underlying pathology. Unfortunately, for many of these diseases it is not clear how changes in gene expression affect pathology. Transcriptome analysis of neurodegenerative diseases using ribonucleic acid sequencing (RNA Seq) and real time quantitative polymerase chain reaction (RT-qPCR) provides for a platform to allow investigators to determine the contribution of various genes to the disease phenotype. In Alzheimer’s disease (AD) there are several candidate genes reported that may be associated with the underlying pathology and are, in addition, alternatively spliced. Thus, AD is an ideal disease to examine how alternative splicing may affect pathology. In this context, genes of particular interest to AD pathology include the amyloid precursor protein (APP), TAU, and apolipoprotein E (APOE). Here, we review the evidence of alternative splicing of these genes in normal and AD patients, and recent therapeutic approaches to control splicing.","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.13188/2376-922X.1000010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66211536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Apolipoprotein E4 an Important Risk Factor for Dementia in Persons with Down Syndrome?","authors":"Troy T Rohn,&nbsp;Katie L McCarty,&nbsp;Julia E Love,&nbsp;Elizabeth Head","doi":"10.13188/2376-922x.1000004","DOIUrl":"https://doi.org/10.13188/2376-922x.1000004","url":null,"abstract":"<p><p>Down syndrome is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Triplication of all or part of human chromosome 21 has been considered as the main cause of Down syndrome. Due to the location of the amyloid precursor protein on chromosome 21, many of the neuropathological features of early-onset Alzheimer's disease including senile plaques and neurofibrillary tangles are also present in Down syndrome patients who are either demented or nondemented. Significant advances in medical treatment have increased longevity in people with Down syndrome resulting in an increased population that may be subjected to many of the same risk factors as those with Alzheimer's disease. It is well established that harboring one or both apolipoprotein E4 alleles greatly increases the risk for Alzheimer's disease. However, whether apolipoprotein E4 contributes to an earlier onset of dementia or increased mortality in Down syndrome patients is still a matter of debate. The purpose of this mini review is to provide an updated assessment on apolipoprotein E4 status and risk potential of developing dementia and mortality associated with Down syndrome.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291017/pdf/nihms652253.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32978922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Broad Impact of TOM40 on Neurodegenerative Diseases in Aging.","authors":"William K Gottschalk,&nbsp;Michael W Lutz,&nbsp;Yu Ting He,&nbsp;Ann M Saunders,&nbsp;Daniel K Burns,&nbsp;Allen D Roses,&nbsp;Ornit Chiba-Falek","doi":"10.13188/2376-922X.1000003","DOIUrl":"https://doi.org/10.13188/2376-922X.1000003","url":null,"abstract":"<p><p>Mitochondrial dysfunction is an important factor in the pathogenesis of age-related diseases, including neurodegenerative diseases like Alzheimer's and Parkinson's spectrum disorders. A polymorphism in Translocase of the Outer Mitochondrial Membrane - 40 kD (<i>TOMM40</i>) is associated with risk and age-of onset of late-onset AD, and is the only nuclear- encoded gene identified in genetic studies to date that presumably contributes to LOAD-related mitochondria dysfunction. In this review, we describe the TOM40-mediated mitochondrial protein import mechanism, and discuss the evidence linking TOM40 with Alzheimer's (AD) and Parkinson's (PD) diseases. All but 36 of the >~1,500 mitochondrial proteins are encoded by the nucleus and are synthesized on cytoplasmic ribosomes, and most of these are imported into mitochondria through the TOM complex, of which TOM40 is the central pore, mediating communication between the cytoplasm and the mitochondrial interior. APP enters and obstructs the TOM40 pore, inhibiting import of OXPHOS-related proteins and disrupting the mitochondrial redox balance. Other pathogenic proteins, such as Aβ and alpha-synuclein, readily pass through the pore and cause toxic effects by directly inhibiting mitochondrial enzymes. Healthy mitochondria normally import and degrade the PD-related protein Pink1, but Pink1 exits mitochondria if the membrane potential collapses and initiates Parkin-mediated mitophagy. Under normal circumstances, this process helps clear dysfunctional mitochondria and contributes to cellular health, but PINK1 mutations associated with PD exit mitochondria with intact membrane potentials, disrupting mitochondrial dynamics, leading to pathology. Thus, TOM40 plays a central role in the mitochondrial dysfunction that underlies age-related neurodegenerative diseases. Learning about the factors that control TOM40 levels and activity, and how TOM40, specifically, and the TOM complex, generally, interacts with potentially pathogenic proteins, will provide deeper insights to AD and PD pathogenesis, and possibly new targets for preventative and/or therapeutic treatments.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.13188/2376-922X.1000003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33108080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Cholesterol Intracellular Trafficking and the Development of Pathological Hallmarks of Sporadic AD.","authors":"Xuesong Chen,&nbsp;Liang Hui,&nbsp;Mahmoud L Soliman,&nbsp;Jonathan D Geiger","doi":"10.13188/2376-922x.1000002","DOIUrl":"https://doi.org/10.13188/2376-922x.1000002","url":null,"abstract":"<p><p>Compared to the rare familial early onset Alzheimer's disease (AD) that results from gene mutations in AbPP and presenilin-1, the pathogenesis of sporadic AD is much more complex and is believed to result from complex interactions between nutritional, environmental, epigenetic and genetic factors. Among those factors, the presence APOE4 is still the single strongest genetic risk factor for sporadic AD. However, the exact underlying mechanism whereby apoE4 contributes to the pathogenesis of sporadic AD remains unclear. Here, we discuss how altered cholesterol intracellular trafficking as a result of apoE4 might contribute to the development of pathological hallmarks of AD including brain deposition of amyloid beta (Ab), neurofibrillary tangles, and synaptic dysfunction.</p>","PeriodicalId":90615,"journal":{"name":"Journal of Parkinson's disease and Alzheimer's disease","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302957/pdf/nihms641125.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33003517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}