scholarly journals MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1443 ◽  
Author(s):  
Maria Serpente ◽  
Chiara Fenoglio ◽  
Marianna D’Anca ◽  
Marina Arcaro ◽  
Federica Sorrentino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Healthy Subjects ◽  
Micro Rna ◽  
Parental Origin ◽  
Total Plasma ◽  
Mirna Signature ◽  
The Central Nervous System

Small extracellular vesicles (EVs) are able to pass from the central nervous system (CNS) into peripheral blood and contain molecule markers of their parental origin. The aim of our study was to isolate and characterize total and neural-derived small EVs (NDEVs) and their micro RNA (miRNA) cargo in Alzheimer’s disease (AD) patients. Small NDEVs were isolated from plasma in a population consisting of 40 AD patients and 40 healthy subjects (CTRLs) using high throughput Advanced TaqMan miRNA OpenArrays®, which enables the simultaneous determination of 754 miRNAs. MiR-23a-3p, miR-223-3p, miR-100-3p and miR-190-5p showed a significant dysregulation in small NDEVs from AD patients as compared with controls (1.16 ± 0.49 versus 7.54 ± 2.5, p = 0.026; 9.32 ± 2.27 versus 0.66 ± 0.18, p <0.0001; 0.069 ± 0.01 versus 0.5 ± 0.1, p < 0.0001 and 2.9 ± 1.2 versus 1.93 ± 0.9, p < 0.05, respectively). A further validation analysis confirmed that miR-23a-3p, miR-223-3p and miR-190a-5p levels in small NDEVs from AD patients were significantly upregulated as compared with controls (p = 0.008; p = 0.016; p = 0.003, respectively) whereas miR-100-3p levels were significantly downregulated (p = 0.008). This is the first study that carries out the comparison between total plasma small EV population and NDEVs, demonstrating the presence of a specific AD NDEV miRNA signature.

scholarly journals Changes of Myelin Organization in Patients with Alzheimer’s Disease Shown by q-Space Myelin Map Imaging

2019 ◽  
Vol 9 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Miho Ota ◽  
Noriko Sato ◽  
Yukio Kimura ◽  
Yoko Shigemoto ◽  
Hiroshi Kunugi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Subjects ◽  
Clinical Symptoms ◽  
Imaging Modality ◽  
Significant Negative Correlation ◽  
Anterior Cingulate ◽  
Resonance Imaging ◽  
Duration Of Illness ◽  
The Central Nervous System

Background: Recent studies detected the aberrant myelination of the central nervous system (CNS) in Alzheimer’s disease (AD). Here, we compared the change of myelination between patients with AD and controls by a novel magnetic resonance imaging modality, “q-space myelin map (MM) imaging.” Methods: Twenty patients with AD and 18 healthy subjects underwent MM imaging. We compared the MM metric between the 2 groups and examined the relationships between the metric and the clinical symptoms of AD. Results: AD patients showed a significant reduction of MM metric in the hippocampus, insula, precuneus, and anterior cingulate regions. There was also a significant negative correlation between the duration of illness and the MM metric in the temporoparietal region. Conclusion: Our findings suggest that MM imaging could be a clinically proper modality to estimate the myelination changes in AD patients.

scholarly journals Enrichment of neurodegenerative microglia signature in brain-derived extracellular vesicles isolated from Alzheimer’s disease mouse model

2020 ◽  
Author(s):  
Satoshi Muraoka ◽  
Mark P. Jedrychowski ◽  
Naotoshi Iwahara ◽  
Mohammad Abdullah ◽  
Kristen D. Onos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Disease Spread ◽  
Proteomic Profiling ◽  
Cellular Origin ◽  
Tandem Mass Tag ◽  
Significant Enrichment ◽  
The Central Nervous System ◽  
Shed Light

AbstractExtracellular vesicles (EVs) are secreted by any neuronal cells in the central nervous system (CNS) for molecular clearance, cellular communications and disease spread in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), although their exact molecular mechanism is poorly understood. We hypothesize that high-resolution proteomic profiling of EVs separated from animal models of AD would determine the composition of EV contents and their cellular origin. Here, we examined recently developed transgenic mice (CAST.APP/PS1), which express familial AD-linked mutations of amyloid precursor protein (APP) and presenilin-1 (PS1) in the CAST/EiJ mouse strain and develop hippocampal neurodegeneration. Quantitative proteomics analysis of EVs separated from CAST.APP/PS1 and age-matched control mice by tandem mass tag-mass spectrometry identified a total of 3,444 unique proteins, which are enriched in neuron, astrocyte, oligodendrocyte and microglia-specific molecules. CAST.APP/PS1-derived EVs show significant enrichment of Psen1, APP, Itgax, and reduction of Wdr61, Pmpca, Aldh1a2, Calu, Anp32b, Actn4 and Ndufv2 compared to WT-derived EVs, suggesting the involvement of Aβ-processing complex and disease-associated / neurodegenerative microglia (DAM/MGnD) in EV secretion. In addition, Itgax and Apoe, the DAM/MGnD markers, in EV show a positive correlation with Itgax and Apoe mRNA expression from brain tissue in CAST.APP/PS1 mice. These datasets indicate the significant contribution of Aβ plaque and neurodegeneration-induced DAM/MGnD microglia for EV secretion in CAST.APP/PS1 mice and shed light on understanding the AD pathogenesis.

Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 842-843
Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Paired Helical Filaments ◽  
Ethanol Intoxication ◽  
Drg Neurons ◽  
Critical Difference ◽  
Suitable Animal Model ◽  
The Central Nervous System ◽  
Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Sustained Drug Release ◽  
Physiochemical Properties ◽  
Conventional Drug ◽  
Health Care Burden ◽  
The Central Nervous System ◽  
Effective Drugs

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.

Neuropeptides in Alzheimer’s Disease: An Update

2019 ◽  
Vol 16 (6) ◽  
pp. 544-558 ◽  
Author(s):  
Carla Petrella ◽  
Maria Grazia Di Certo ◽  
Christian Barbato ◽  
Francesca Gabanella ◽  
Massimo Ralli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Potential Role ◽  
Brain Distribution ◽  
Brain Areas ◽  
Small Proteins ◽  
Current Review ◽  
The Central Nervous System ◽  
Available Information

Neuropeptides are small proteins broadly expressed throughout the central nervous system, which act as neurotransmitters, neuromodulators and neuroregulators. Growing evidence has demonstrated the involvement of many neuropeptides in both neurophysiological functions and neuropathological conditions, among which is Alzheimer’s disease (AD). The role exerted by neuropeptides in AD is endorsed by the evidence that they are mainly neuroprotective and widely distributed in brain areas responsible for learning and memory processes. Confirming this point, it has been demonstrated that numerous neuropeptide-containing neurons are pathologically altered in brain areas of both AD patients and AD animal models. Furthermore, the levels of various neuropeptides have been found altered in both Cerebrospinal Fluid (CSF) and blood of AD patients, getting insights into their potential role in the pathophysiology of AD and offering the possibility to identify novel additional biomarkers for this pathology. We summarized the available information about brain distribution, neuroprotective and cognitive functions of some neuropeptides involved in AD. The main focus of the current review was directed towards the description of clinical data reporting alterations in neuropeptides content in both AD patients and AD pre-clinical animal models. In particular, we explored the involvement in the AD of Thyrotropin-Releasing Hormone (TRH), Cocaine- and Amphetamine-Regulated Transcript (CART), Cholecystokinin (CCK), bradykinin and chromogranin/secretogranin family, discussing their potential role as a biomarker or therapeutic target, leaving the dissertation of other neuropeptides to previous reviews.

scholarly journals Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ding ◽  
Jin Wang ◽  
Miaoxin Huang ◽  
Zhangpeng Chen ◽  
Jing Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Knock Out ◽  
Classical Complement Pathway ◽  
Synaptic Remodeling ◽  
The Central Nervous System ◽  
System Activation ◽  
Knock Out Mice ◽  
Synaptic Pruning

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.

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