Higher levels of lysosomal associated membrane protein-2 (LAMP-2) in plasma exosomes from Alzheimer’s disease: An exploratory study from South India (original) (raw)
Related papers
Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease
Neurology, 2015
Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy. Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker. Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p ≤ 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia (p ≤ 0.0...
Alzheimer's & Dementia, 2014
Background: Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Methods: Blood exosomes obtained at one time-point from patients with AD (n 5 57) or frontotemporal dementia (FTD) (n 5 16), and at two time-points from others (n 5 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays. Results: Mean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid b 1-42 (Ab1-42) for AD and levels of P-T181-tau and Ab1-42 for FTD were significantly higher than for case-controls.
Plasma neuronal exosomal levels of Alzheimer's disease biomarkers in normal aging
Annals of clinical and translational neurology, 2016
Plasma neuronal exosomal levels of pathogenic Alzheimer's disease (AD) proteins, cellular survival factors, and lysosomal proteins distinguish AD patients from control subjects, but changes in these exosomal proteins associated with normal aging have not been described for cognitively intact subjects. Plasma neuronal exosomal levels of P-T181-tau, P-S396-tau, Aβ 1-42, cathepsin D, repressor element 1-silencing transcription factor, and neurogranin were quantified longitudinally in cognitively intact older adults using two samples collected at 3- to 11-year intervals. Except for P-S396-tau, exosomal protein levels changed significantly with aging, but were largely outside the range observed in AD patients.
Exosomes as possible spread factor and potential biomarkers in Alzheimer's disease: current concepts
Biomarkers in Medicine, 2018
Increasing evidence points that important factors during development/spread of Alzheimer's disease in brain tissue are small extracellular vesicles, called exosomes. Exosomes comprise disease-related biomolecules such as the amyloid protein precursor, β-amyloid peptide and tau protein. Exosomes are hypothesized to facilitate the spread of β-amyloid peptide and tau protein from their cells of origin (e.g., neurons) to the extracellular space and to recipient cells to alter their phenotype and function. The roles of exosomes carry a rich biomolecules cargo in physiology and pathology is poorly understood. In this review, we will consider new information about the role of exosomes in Alzheimer's disease spreading and progression and underline their possible usefulness as the future diagnostic antemortem biomarkers in this devastating disorder.
Plasma Neuronal Exosomal Levels of Alzheimer\u27s Disease Biomarkers in Normal Aging
2016
Plasma neuronal exosomal levels of pathogenic Alzheimer\u27s disease (AD) proteins, cellular survival factors, and lysosomal proteins distinguish AD patients from control subjects, but changes in these exosomal proteins associated with normal aging have not been described for cognitively intact subjects. Plasma neuronal exosomal levels of P-T181-tau, P-S396-tau, Aβ1-42, cathepsin D, repressor element 1-silencing transcription factor, and neurogranin were quantified longitudinally in cognitively intact older adults using two samples collected at 3- to 11-year intervals. Except for P-S396-tau, exosomal protein levels changed significantly with aging, but were largely outside the range observed in AD patients
Molecular Neurobiology, 2022
Exosomes are small extracellular vesicles (EVs) present in human biofluids that can transport specific disease-associated molecules. Consequently blood-derived exosomes have emerged as important peripheral biomarker sources for a wide range of diseases, among them Alzheimer's disease (AD). Although there is no effective cure for AD, an accurate diagnosis, relying on easily accessible peripheral biofluids, is still necessary to discriminate this disease from other dementias, test potential therapies and even monitor rate of disease progression. The ultimate goal is to produce a cost-effective and widely available alternative, which can also be employed as a first clinical screen. In this study, EVs with exosome-like characteristics were isolated from serum of Controls and AD cases through precipitation-and column-based methods, followed by mass spectrometry analysis. The resulting proteomes were characterized by Gene Ontology (GO) and multivariate analyses. Although GO terms were similar for exosomes' proteomes of Controls and ADs, using both methodologies, a clear segregation of disease cases was obtained when using the precipitation-based method. Nine significantly different abundant proteins were identified between Controls and AD cases, representing putative biomarker candidate targets. Among them are AACT and C4BPα, two Aβ-binding proteins, whose exosome levels were further validated in individuals from independent cohorts using antibody-based approaches. The findings discussed represent an important contribution to the identification of novel exosomal biomarker candidates useful as potential blood-based tools for AD diagnosis.
2021
Exosomes are small extracellular vesicles (EVs) present in human biofluids that can transport specific disease-associated molecules. Consequently blood-derived exosomes have emerged as important peripheral biomarker sources for a wide range of diseases, among them Alzheimer’s disease (AD). Although there is no effective cure for AD, an accurate diagnosis, relying on easily accessible peripheral biofluids, is still necessary to discriminate this disease from other dementias, test potential therapies and even monitor rate of disease progression. The ultimate goal is to produce a cost-effective and widely available alternative, which can also be employed as a first clinical screen. In this study, EVs with exosome-like characteristics were isolated from serum of Controls and AD cases through precipitation- and column-based methods, followed by mass spectrometry analysis. The resulting proteomes were characterized by Gene Ontology (GO) functional enrichment and multivariate analyses. Alt...
International Journal of Molecular Sciences
Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson’s and Alzheimer’s disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers have harnessed EXOs in drug delivery applications. EXOs have shown low immunogenicity as natural drug delivery vehicles, thus ensuring efficient drug delivery without causing significant adverse reactions. Recently, EXOs provided potential drug delivery opportunities in AD and promising future clinical applications with the diagnosis of NDD and were studied for their usefulness in disease detection and prediction prior to the emergence of symptoms. In the future, the microfluidics technique will play an essential role in isolating and detecting EXOs to diagnose AD before the development of advanced symptoms. This review is not reiterative literature but will discuss why E...
International Journal of Molecular Sciences
The potential of exosomes as biomarker resources for diagnostics and even for therapeutics has intensified research in the field, including in the context of Alzheimer´s disease (AD). The search for disease biomarkers in peripheral biofluids is advancing mainly due to the easy access it offers. In the study presented here, emphasis was given to the bioinformatic identification of putative exosomal candidates for AD. The exosomal proteomes of cerebrospinal fluid (CSF), serum and plasma, were obtained from three databases (ExoCarta, EVpedia and Vesiclepedia), and complemented with additional exosomal proteins already associated with AD but not found in the databases. The final biofluids’ proteomes were submitted to gene ontology (GO) enrichment analysis and the exosomal Aβ-binding proteins that can constitute putative candidates were identified. Among these candidates, gelsolin, a protein known to be involved in inhibiting Abeta fibril formation, was identified, and it was tested in h...
Therapeutic role of MSCs-derived exosomes for Alzheimer's disease
Journal of Scientific Research in Science, 2020
The discovery of mesenchymal stem cell-derived exosomes (MSCs-derived exosomes) has shed a new light in the development of disease-modifying treatments for Alzheimer (AD). The present study is an attempt to investigate the influence of these extracellular vesicles (exosomes) in Alz therapy. A total of 38 adult female albino Wistar rats were randomly assigned to the following groups: Control group (C) of 8 rats given saline; Alzheimer's group (Alz) of 15 ovariectomized animals inoculated orally with AlCl3 (17mg/Kg b.wt/day) for 2 months after 6 weeks of surgical operation and 15 Alzheimer's disease-induced rats treated (i.v) with (10 7 MSCs-derived exosomes/rat/week). After 2 and 4 weeks animals were sacrificed by ether inhalation anesthesia where brains were removed and processed for histological investigation by Hx&E and biochemical analysis for measuring β-Amyloid 1-42 and Brain derived neurotrophic factor (BDNF) levels.