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Exosome dementia

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https://www.readbyqxmd.com/read/29025866/declining-levels-of-functionally-specialized-synaptic-proteins-in-plasma-neuronal-exosomes-with-progression-of-alzheimer-s-disease
#1
Edward J Goetzl, Erin L Abner, Gregory A Jicha, Dimitrios Kapogiannis, Janice B Schwartz
Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2α (NRXN2α), with their respective postsynaptic functional partners, GluA4-containing glutamate (AMPA4) receptor and neuroligin 1 (NLGN1), enhance excitatory synaptic activity in some areas of the hippocampus and cerebral cortex. As early damage of such excitatory circuits in the brain tissues of participants with Alzheimer's disease (AD) correlates with cognitive losses, plasma neuron-derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics...
October 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28963439/neuroprotective-astrocyte-derived-insulin-insulin-like-growth-factor-1-stimulates-endocytic-processing-and-extracellular-release-of-neuron-bound-a%C3%AE-oligomers
#2
Jason Pitt, Kyle C Wilcox, Vanessa Tortelli, Luan Pereira Diniz, Maira S Oliveira, Cassandra Dobbins, Xiao-Wen Yu, Sathwik Nandamuri, Flávia C A Gomes, Nadia DiNunno, Kirsten L Viola, Fernanda G De Felice, Sergio T Ferreira, William L Klein
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AβOs. Here we employed physically separated neuron-astrocyte cocultures to investigate potential non-cell autonomous neuroprotective factors influencing AβO toxicity...
October 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28882786/exosomal-biomarkers-in-down-syndrome-and-alzheimer-s-disease
#3
REVIEW
Eric D Hamlett, Aurélie Ledreux, Huntington Potter, Heidi J Chial, David Patterson, Joaquin M Espinosa, Brianne M Bettcher, Ann-Charlotte Granholm
Every person with Down syndrome (DS) has the characteristic features of Alzheimer's disease (AD) neuropathology in their brain by the age of forty, and most go on to develop AD dementia. Since people with DS show highly variable levels of baseline function, it is often difficult to identify early signs of dementia in this population. The discovery of blood biomarkers predictive of dementia onset and/or progression in DS is critical for developing effective clinical diagnostics. Our recent studies show that neuron-derived exosomes, which are small extracellular vesicles secreted by most cells in the body, contain elevated levels of amyloid-beta peptides and phosphorylated-Tau that could indicate a preclinical AD phase in people with DS starting in childhood...
September 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28794261/neuroprotective-astrocyte-derived-insulin-igf-1-stimulate-endocytic-processing-and-extracellular-release-of-neuron-bound-a%C3%AE-oligomers
#4
Jason Pitt, Kyle C Wilcox, Vanessa Tortelli, Luan Pereira Diniz, Maira S Oliveira, Cassandra Dobbins, Xiao-Wen Yu, Sathwik Nandamuri, Flávia C A Gomes, Nadia DiNunno, Kirsten L Viola, Fernanda G De Felice, Sergio T Ferreira, William L Klein
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AβOs. Here we employed physically-separated neuron-astrocyte co-cultures to investigate potential non cell-autonomous neuroprotective factors influencing AβO toxicity...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28722658/the-golgi-localized-gamma-ear-containing-arf-binding-gga-protein-family-alters-alpha-synuclein-%C3%AE-syn-oligomerization-and-secretion
#5
Bjoern von Einem, Judith Eschbach, Martin Kiechle, Anke Wahler, Dietmar R Thal, Pamela J McLean, Jochen H Weishaupt, Albert C Ludolph, Christine A F von Arnim, Karin M Danzer
Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase α-syn secretion...
July 15, 2017: Aging
https://www.readbyqxmd.com/read/28684681/interplay-between-autophagy-exosomes-and-hiv-1-associated-neurological-disorders-new-insights-for-diagnosis-and-therapeutic-applications
#6
REVIEW
Chet Raj Ojha, Jessica Lapierre, Myosotys Rodriguez, Seth M Dever, Mohammad Asad Zadeh, Catherine DeMarino, Michelle L Pleet, Fatah Kashanchi, Nazira El-Hage
The autophagy-lysosomal pathway mediates a degradative process critical in the maintenance of cellular homeostasis as well as the preservation of proper organelle function by selective removal of damaged proteins and organelles. In some situations, cells remove unwanted or damaged proteins and RNAs through the release to the extracellular environment of exosomes. Since exosomes can be transferred from one cell to another, secretion of unwanted material to the extracellular environment in exosomes may have an impact, which can be beneficial or detrimental, in neighboring cells...
July 6, 2017: Viruses
https://www.readbyqxmd.com/read/28610892/novel-human-neuronal-tau-model-exhibiting-neurofibrillary-tangles-and-transcellular-propagation
#7
Patrick Reilly, Charisse N Winston, Kelsey R Baron, Margarita Trejo, Edward M Rockenstein, Johnny C Akers, Najla Kfoury, Marc Diamond, Eliezer Masliah, Robert A Rissman, Shauna H Yuan
Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy, which are associated with the pathological aggregation of tau protein into neurofibrillary tangles (NFT). Studies have characterized tau as a "prion-like" protein given its ability to form distinct, stable amyloid conformations capable of transcellular and multigenerational propagation in clonal fashion. It has been proposed that progression of tauopathy could be due to the prion-like propagation of tau, suggesting the possibility that end-stage pathologies, like NFT formation, may require an instigating event such as tau seeding...
October 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28599681/brain-derived-exosomes-from-dementia-with-lewy-bodies-propagate-%C3%AE-synuclein-pathology
#8
Jennifer Ngolab, Ivy Trinh, Edward Rockenstein, Michael Mante, Jazmin Florio, Margarita Trejo, Deborah Masliah, Anthony Adame, Eliezer Masliah, Robert A Rissman
Proteins implicated in neurodegenerative conditions such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have been identified in bodily fluids encased in extracellular vesicles called exosomes. Whether exosomes found in DLB patients can transmit pathology is not clear. In this study, exosomes were successfully harvested through ultracentrifugation from brain tissue from DLB and AD patients as well as non-diseased brain tissue. Exosomes extracted from brains diagnosed with either AD or DLB contained aggregate-prone proteins...
June 9, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28253991/micrornas-as-peripheral-biomarkers-in-aging-and-age-related-diseases
#9
REVIEW
S Kumar, M Vijayan, J S Bhatti, P H Reddy
MicroRNAs (miRNAs) are found in the circulatory biofluids considering the important molecules for biomarker study in aging and age-related diseases. Blood or blood components (serum/plasma) are primary sources of circulatory miRNAs and can release these in cell-free form either bound with some protein components or encapsulated with microvesicle particles, called exosomes. miRNAs are quite stable in the peripheral circulation and can be detected by high-throughput techniques like qRT-PCR, microarray, and sequencing...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28241427/potential-modes-of-intercellular-%C3%AE-synuclein-transmission
#10
REVIEW
Dario Valdinocci, Rowan A W Radford, Sue Maye Siow, Roger S Chung, Dean L Pountney
Intracellular aggregates of the α-synuclein protein result in cell loss and dysfunction in Parkinson's disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as α-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby α-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of α-synuclein as the major mode of disease propagation between brain regions during disease progression...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28219659/dementia-like-pathology-in-type-2-diabetes-a-novel-microrna-mechanism
#11
Anuradha Kalani, Pankaj Chaturvedi, Claudio Maldonado, Philip Bauer, Irving G Joshua, Suresh C Tyagi, Neetu Tyagi
Although type-2 diabetes (T2D) has been reported to increase the risk of cognitive dysfunction and dementia, the underlying mechanisms remain unclear. Dementia-like pathology is attributed to the accumulation of cellular prion protein (PrP(c)) which plays a role in cognitive dysfunction. However, its involvement and regulation in diabetic dementia-like pathology is not well understood. Using T2D db/db (leptin receptor knockout) mice subjected to object recognition and Y-maze behavioral tests, we determined that short-term memory was compromised and that the mice displayed abrupt spontaneous behaviour compared to db/m control mice...
April 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28184302/the-role-of-exosomes-in-the-pathogenesis-of-alzheimer-disease
#12
REVIEW
Tingting Xiao, Weiwei Zhang, Bin Jiao, Chu-Zheng Pan, Xixi Liu, Lu Shen
Exosomes are small vesicles secreted by most cell types including neurons that function in intercellular communication through transfer of their cargo or encapsulate and eliminate unnecessary cellular components and therefore have a broad impact on nerve development, activation and regeneration. In addition, exosomes have been observed to be involved in spreading pathological misfolded proteins, thereby leading to the onset and propagation of disease. Alzheimer disease (AD) is the most common form of dementia and characterized by two types of lesions: amyloid plaques and neurofibrillary tangles...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27755974/neuronal-exosomes-reveal-alzheimer-s-disease-biomarkers-in-down-syndrome
#13
Eric D Hamlett, Edward J Goetzl, Aurélie Ledreux, Vitaly Vasilevko, Heather A Boger, Angela LaRosa, David Clark, Steven L Carroll, María Carmona-Iragui, Juan Fortea, Elliott J Mufson, Marwan Sabbagh, Abdul H Mohammed, Dean Hartley, Eric Doran, Ira T Lott, Ann-Charlotte Granholm
INTRODUCTION: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD. METHODS: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls...
May 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27732842/cell-to-cell-transmission-of-dipeptide-repeat-proteins-linked-to-c9orf72-als-ftd
#14
Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti
Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27601437/decreased-synaptic-proteins-in-neuronal-exosomes-of-frontotemporal-dementia-and-alzheimer-s-disease
#15
Edward J Goetzl, Dimitrios Kapogiannis, Janice B Schwartz, Iryna V Lobach, Laura Goetzl, Erin L Abner, Gregory A Jicha, Anna M Karydas, Adam Boxer, Bruce L Miller
Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD). Plasma neuronal-derived exosomes (NDEs) were recovered by precipitation and immunoabsorption from 12 patients with AD, 16 with FTD, and 28 controls in a cross-sectional study, and from 9 patients with AD, 10 with FTD, and 19 controls in a longitudinal study. Six synaptic proteins in NDE extracts were quantified by ELISAs and normalized for exosome amounts...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27511944/cargo-proteins-of-plasma-astrocyte-derived-exosomes-in-alzheimer-s-disease
#16
Edward J Goetzl, Maja Mustapic, Dimitrios Kapogiannis, Erez Eitan, Irina V Lobach, Laura Goetzl, Janice B Schwartz, Bruce L Miller
Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic and pathologic roles have not been well defined for this pathway. The capacity to isolate immunochemically human plasma neuron-derived exosomes (NDEs), containing neuron-specific cargo, has permitted characterization of CNS-derived exosomes in living humans. Constituents of the amyloid β-peptide (Aβ)42-generating system now are examined in 2 distinct sets of human neural cells by quantification in astrocyte-derived exosomes (ADEs) and NDEs, enriched separately from plasmas of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD) and matched cognitively normal controls...
November 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27460707/proteomic-analysis-of-fus-interacting-proteins-provides-insights-into-fus-function-and-its-role-in-als
#17
Marisa Kamelgarn, Jing Chen, Lisha Kuang, Alexandra Arenas, Jianjun Zhai, Haining Zhu, Jozsef Gal
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Mutations in the Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) gene cause a subset of familial ALS cases and are also implicated in sporadic ALS. FUS is typically localized to the nucleus. The ALS-related FUS mutations cause cytoplasmic mis-localization and the formation of stress granule-like structures. Abnormal cytoplasmic FUS localization was also found in a subset of frontotemporal dementia (FTLD) cases without FUS mutations...
October 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27408937/prediction-of-conversion-from-mild-cognitive-impairment-to-dementia-with-neuronally-derived-blood-exosome-protein-profile
#18
Charisse N Winston, Edward J Goetzl, Johnny C Akers, Bob S Carter, Edward M Rockenstein, Douglas Galasko, Eliezer Masliah, Robert A Rissman
INTRODUCTION: Levels of Alzheimer's disease (AD)-related proteins in plasma neuronal derived exosomes (NDEs) were quantified to identify biomarkers for prediction and staging of mild cognitive impairment (MCI) and AD. METHODS: Plasma exosomes were extracted, precipitated, and enriched for neuronal source by anti-L1CAM antibody absorption. NDEs were characterized by size (Nanosight) and shape (TEM) and extracted NDE protein biomarkers were quantified by ELISAs. Plasma NDE cargo was injected into normal mice, and results were characterized by immunohistochemistry to determine pathogenic potential...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/27102354/bone-marrow-derived-mesenchymal-stem-cells-improve-diabetes-induced-cognitive-impairment-by-exosome-transfer-into-damaged-neurons-and-astrocytes
#19
Masako Nakano, Kanna Nagaishi, Naoto Konari, Yuki Saito, Takako Chikenji, Yuka Mizue, Mineko Fujimiya
The incidence of dementia is higher in diabetic patients, but no effective treatment has been developed. This study showed that rat bone marrow mesenchymal stem cells (BM-MSCs) can improve the cognitive impairments of STZ-diabetic mice by repairing damaged neurons and astrocytes. The Morris water maze test demonstrated that cognitive impairments induced by diabetes were significantly improved by intravenous injection of BM-MSCs. In the CA1 region of the hippocampus, degeneration of neurons and astrocytes, as well as synaptic loss, were prominent in diabetes, and BM-MSC treatment successfully normalized them...
April 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26974972/enabling-metabolomics-based-biomarker-discovery-studies-using-molecular-phenotyping-of-exosome-like-vesicles
#20
Tatiana Altadill, Irene Campoy, Lucia Lanau, Kirandeep Gill, Marina Rigau, Antonio Gil-Moreno, Jaume Reventos, Stephen Byers, Eva Colas, Amrita K Cheema
Identification of sensitive and specific biomarkers with clinical and translational utility will require smart experimental strategies that would augment expanding the breadth and depth of molecular measurements within the constraints of currently available technologies. Exosomes represent an information rich matrix to discern novel disease mechanisms that are thought to contribute to pathologies such as dementia and cancer. Although proteomics and transcriptomic studies have been reported using Exosomes-Like Vesicles (ELVs) from different sources, exosomal metabolome characterization and its modulation in health and disease remains to be elucidated...
2016: PloS One
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