A Pilot Study of Urinary Exosomes in Alzheimer’s Disease

2019 ◽  
Vol 19 (5-6) ◽  
pp. 184-191 ◽  
Author(s):  
Ruihua Sun ◽  
Huayuan Wang ◽  
Yingying Shi ◽  
Dandan Gao ◽  
Zhikun Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Subjects ◽  
Neuronal Loss ◽  
Cell Types ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Protein Levels ◽  
Transmission Electron ◽  
Urinary Exosomes

Background: Exosomes are nano-sized extracellular vesicles secreted by most cell types and abundantly present in body fluids, including blood, saliva, urine, cerebrospinal fluid, and breast milk. Exosomes can spread toxic amyloid-beta (Aβ) and hyperphosphorylated tau between cells, contributing to neuronal loss in Alzheimer’s disease (AD). Objective: To explore changes in the morphology, number, and pathological protein levels of urinary exosomes in AD patients compared with age-matched healthy subjects. Methods: In this study, enzyme-linked immunosorbent assay was used to detect the levels of Aβ1–42 and P-S396-tau (normalized by CD63) in urinary exosomes of AD patients and matched healthy subjects. We used transmission electron microscopy and nanoparticle tracking analysis to observe the exosomes. Results: We found that the levels of Aβ1–42 and P-S396-tau in the urinary exosomes of AD patients were higher than those of matched healthy controls. Exosomes taken from AD patients were more numerous. Conclusion: The differences in levels of Aβ1–42 and P-S396-tau and the quantity of urinary exosomes between AD patients and healthy controls may provide a basis for early diagnosis of AD.

scholarly journals Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer’s disease

2020 ◽  
Vol 47 (13) ◽  
pp. 3176-3185
Author(s):  
Mark E. Schmidt ◽  
Luc Janssens ◽  
Diederik Moechars ◽  
Frederik J. R. Rombouts ◽  
Maarten Timmers ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Subjects ◽  
Graphical Analysis ◽  
Whole Body ◽  
Healthy Controls ◽  
Pet Tracer ◽  
Cortical Regions ◽  
Pet Scans ◽  
Pet Amyloid

Abstract Purpose The accumulation of misfolded tau is a common feature of several neurodegenerative disorders, with Alzheimer’s disease (AD) being the most common. Earlier we identified JNJ-64326067, a novel isoquinoline derivative with high affinity and selectivity for tau aggregates from human AD brain. We report the dosimetry of [18F] JNJ-64326067 and results of a proof-of-concept study comparing subjects with probable Alzheimer’s disease to age-matched healthy controls. Methods [18F] JNJ-64326067 PET scans were acquired for 90 min and then from 120 to 180 min in 5 participants with [18F]-florbetapir PET amyloid positive probable AD (73 ± 9 years) and 5 [18F]-florbetapir PET amyloid negative healthy controls (71 ± 7 years). Whole-body [18F] JNJ-64326067 PET CT scans were acquired in six healthy subjects for 5.5 h in 3 scanning sessions. Brain PET scans were visually reviewed. Regional quantification included kinetic analysis of distribution volume ration (DVR) estimated by Logan graphical analysis over the entire scan and static analysis of SUVr in late frames. Both methods used ventral cerebellar cortex as a reference region. Results One of the healthy controls had focal areas of PET signal in occipital and parietal cortex underlying the site of a gunshot injury as an adolescent; the other four healthy subjects had no tau brain signal. Four of the 5 AD participants had visually apparent retention of [18F] JNJ-64326067 in relevant cortical regions. One of the AD subjects was visually negative. Cortical signal in visually positive subjects approached steady state by 120 min. Temporal and frontal cortical SUVr/DVR values in visually positive AD subjects ranged from 1.21 to 3.09/1.2 to 2.18 and from 0.92 to 1.28/0.91 to 1.16 in healthy controls. Whole-body effective dose was estimated to be 0.0257 mSv/MBq for females and 0.0254 mSv/MBq for males. Conclusions [18F] JNJ-64326067 could be useful for detection and quantitation of tau aggregates.

scholarly journals Suppression of Alzheimer’s Disease-Like Pathology Progression by Mitochondria-Targeted Antioxidant SkQ1: A Transcriptome Profiling Study

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Natalia A. Stefanova ◽  
Nikita I. Ershov ◽  
Nataliya G. Kolosova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Function ◽  
Neuronal Loss ◽  
Transcriptome Profiling ◽  
Synaptic Activity ◽  
Oxys Rats ◽  
Specific Gene ◽  
Rna Seq ◽  
Protein Levels

Alzheimer’s disease (AD) is the most common type of dementia, with increasing prevalence and no disease-modifying treatment available yet. There is increasing evidence—from interventions targeting mitochondria—that may shed some light on new strategies for the treatment of AD. Previously, using senescence-accelerated OXYS rats that simulate key characteristics of sporadic AD, we have shown that treatment with mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from age 12 to 18 months (that is, during active progression of AD-like pathology)—via improvement of mitochondrial function—prevented the neuronal loss and synaptic damage, enhanced neurotrophic supply, and decreased amyloid-β1–42 protein levels and tau hyperphosphorylation in the hippocampus. In the present study, we continued to explore the mechanisms of the anti-AD effects of SkQ1 in an OXYS rat model through deep RNA sequencing (RNA-seq) and focused upon the cell-specific gene expression alterations in the hippocampus. According to RNA-seq results, OXYS rats had 1,159 differentially expressed genes (DEGs) relative to Wistar rats (control), and 6-month treatment with SkQ1 decreased their number twofold. We found that 10.5% of all DEGs in untreated (control) OXYS rats were associated with mitochondrial function, whereas SkQ1 eliminated differences in the expression of 76% of DEGs (93 from 122 genes). Using transcriptome approaches, we found that the anti-AD effects of SkQ1 are associated with an improvement of the activity of many signaling pathways and intracellular processes. SkQ1 changed the expression of genes in neuronal, glial, and endothelial cells, and these genes are related to mitochondrial function, neurotrophic and synaptic activity, calcium processes, immune and cerebrovascular systems, catabolism, degradation, and apoptosis. Thus, RNA-seq analysis yields a detailed picture of transcriptional changes during the development of AD-like pathology and can point to the molecular and genetic mechanisms of action of the agents (including SkQ1) holding promise for the prevention and treatment of AD.

scholarly journals Eosinophil-Derived Neurotoxin Is Elevated in Patients with Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Guan-Ting Liu ◽  
Chi-Shin Hwang ◽  
Chia-Hung Hsieh ◽  
Chih-Hao Lu ◽  
Sunny Li-Yun Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
High Mobility ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Lateral Sclerosis

Background and Objectives. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation have been implicated in the pathophysiology of ALS. Members of the family of damage-associated molecular patterns, including reactive oxygen species, high-mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in pathological conditions. In this study, we aim to discover new biomarker for detecting ALS.Materials and Methods. We examined 44 patients with ALS, 41 patients with Alzheimer’s disease, 41 patients with Parkinson’s disease, and 44 healthy controls. The concentration of serum EDN was measured using an enzyme-linked immunosorbent assay.Results. EDN levels were significantly increased 2.17-fold in the serum of patients with ALS as compared with healthy controls (P<0.05). No correlation between the levels of serum EDN and various clinical parameters of ALS was found. Moreover, the levels of serum EDN in patients with Parkinson’s disease and Alzheimer’s disease and healthy controls were similar.Conclusion. A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of ALS.

scholarly journals Role of Neuron and Glia in Alzheimer’s Disease and Associated Vascular Dysfunction

2021 ◽  
Vol 13 ◽  
Author(s):  
Sanghamitra Bandyopadhyay
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Cell Types ◽  
Cellular Interactions

Amyloidogenicity and vascular dysfunction are the key players in the pathogenesis of Alzheimer’s disease (AD), involving dysregulated cellular interactions. An intricate balance between neurons, astrocytes, microglia, oligodendrocytes and vascular cells sustains the normal neuronal circuits. Conversely, cerebrovascular diseases overlap neuropathologically with AD, and glial dyshomeostasis promotes AD-associated neurodegenerative cascade. While pathological hallmarks of AD primarily include amyloid-β (Aβ) plaques and neurofibrillary tangles, microvascular disorders, altered cerebral blood flow (CBF), and blood-brain barrier (BBB) permeability induce neuronal loss and synaptic atrophy. Accordingly, microglia-mediated inflammation and astrogliosis disrupt the homeostasis of the neuro-vascular unit and stimulate infiltration of circulating leukocytes into the brain. Large-scale genetic and epidemiological studies demonstrate a critical role of cellular crosstalk for altered immune response, metabolism, and vasculature in AD. The glia associated genetic risk factors include APOE, TREM2, CD33, PGRN, CR1, and NLRP3, which correlate with the deposition and altered phagocytosis of Aβ. Moreover, aging-dependent downregulation of astrocyte and microglial Aβ-degrading enzymes limits the neurotrophic and neurogenic role of glial cells and inhibits lysosomal degradation and clearance of Aβ. Microglial cells secrete IGF-1, and neurons show a reduced responsiveness to the neurotrophic IGF-1R/IRS-2/PI3K signaling pathway, generating amyloidogenic and vascular dyshomeostasis in AD. Glial signals connect to neural stem cells, and a shift in glial phenotype over the AD trajectory even affects adult neurogenesis and the neurovascular niche. Overall, the current review informs about the interaction of neuronal and glial cell types in AD pathogenesis and its critical association with cerebrovascular dysfunction.

scholarly journals Ceruloplasmin (2-D PAGE) Pattern and Copper Content in Serum and Brain of Alzheimer Disease Patients

2006 ◽  
Vol 1 ◽  
pp. 117727190600100 ◽  
Author(s):  
Rosanna Squitti ◽  
Carlo C. Quattrocchi ◽  
Gloria Dal Forno ◽  
Piero Antuono ◽  
David R. Wekstein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Weight ◽  
Alzheimer Disease ◽  
Healthy Subjects ◽  
Copper Content ◽  
Copper Homeostasis ◽  
Low Molecular Weight ◽  
Healthy Controls ◽  
The Brain

A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We previously evidenced that an excess of non-ceruloplasmin-copper (NCC) correlated with the main functional, anatomical as well as cerebrospinal markers of the disease. Aim of our study was to investigate ceruloplasmin isoforms as potential actors in this AD copper dysfunction. Our data show that AD patients have ceruloplasmin fragments of low molecular weight (<50 kDa) both in their serum and brain, contrary to healthy controls. Ceruloplasmin isoforms of higher molecular weight (115 and 135 kDa in serum and 135 kDa in brain), as well as copper levels in the brain, instead, do not seem to mark a difference between AD and healthy subjects. These data suggest a ceruloplasmin fragmentation in the serum of AD patients. Some clues in this direction have been found also in the AD brain.

scholarly journals TDP-43 is elevated in plasma neuronal-derived exosomes of patients with Alzheimer's disease

2019 ◽  
Author(s):  
Nan Zhang ◽  
Dongmei Gu ◽  
Meng Meng ◽  
Marc L. Gordon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Oldest Old ◽  
Neuropsychiatric Symptoms ◽  
Apoe Genotype ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amyloid Pet ◽  
Healthy Controls

Abstract Background Recently, TDP-43 has been recognized as a common proteinopathy in the “oldest old” and a neuropathological comorbidity in patients with Alzheimer’s disease (AD). However, since it has a low concentration in cerebrospinal fluid, the presence of TDP-43 in AD is rarely investigated in vivo. Methods Twenty-four patients with amyloid PET confirmed AD and 15 healthy controls (HCs) were included in this study. TDP-43 level in plasma neuronal-derived exosomes (NDEs) was measured by enzyme-linked immunosorbent assay. Results TDP-43 level was elevated in patients with AD compared with HCs (1.20 ± 0.91 ng/ml vs 0.64 ± 0.20 ng/ml, P < 0.039), after controlling for age. There was no correlation between TDP-43 level and cognitive function, neuropsychiatric symptoms or APOE genotype in patients with AD. Conclusions This study demonstrated increased TDP-43 accumulation in AD patients by examining plasma NDEs, which may provide a window into the effects of TDP-43 on AD progression.

scholarly journals Elevated Osteopontin Levels in Mild Cognitive Impairment and Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yuan Sun ◽  
Xue Song Yin ◽  
Hong Guo ◽  
Rong Kun Han ◽  
Rui Dong He ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neurologic Diseases ◽  
Protein Levels ◽  
Wide Scale ◽  
Shed Light

Inflammatory mediators are closely associated with the pathogenesis of neurodegenerative changes in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Osteopontin (OPN) is a proinflammatory cytokine that has been shown to play an important role in various neuroinflammatory diseases. However, the function of OPN in AD and MCI progression is not well defined. Cerebrospinal fluid (CSF) and plasma samples were obtained from 35 AD patients, 31 MCI patients, and 20 other noninflammatory neurologic diseases (OND). Concentrations of OPN in the CSF and plasma were determined by enzyme-linked immunosorbent assay. During a 3-year clinical followup, 13 MCI patients converted to AD (MCI converters), and 18 were clinically stable (MCI nonconverters). CSF OPN concentrations were significantly increased in AD and MCI converters compared to OND, and increased levels of OPN in AD were associated with MMSE score; OPN protein levels both in the CSF and plasma of newly diagnosed AD patients were higher than that of chronical patients. In MCI converters individuals tested longitudinally, both plasma and CSF OPN concentrations were significantly elevated when they received a diagnosis of AD during followup. Further wide-scale studies are necessary to confirm these results and to shed light on the etiopathogenic role of osteopontin in AD.

scholarly journals The Relationship between Serum Endocan Levels and Depression in Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Kyung Hee Yoon ◽  
So Yeon Kim ◽  
Yoo Sun Moon ◽  
Daeyoung Roh ◽  
Sang Kyu Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Short Form ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Korean Version ◽  
State Examination

Objectives. Growing evidence suggests that angiogenic vascular factors may be involved in the pathogenic mechanism of Alzheimer’s disease (AD), and recently endocan has been proposed as an angiogenic biomarker. The aim of this study was to measure serum endocan levels according to the presence of depression in AD and to investigate the association among the serum endocan levels, cognitive function, and depression in these patients.Methods. Serum endocan levels were measured in 26 AD patients with depression, 29 AD patients without depression, and 29 healthy controls using an enzyme-linked immunosorbent assay kit. The Mini-Mental State Examination-Korean version (MMSE-KC) and the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) were used to evaluate cognitive function and depressive symptoms, respectively.Results. Serum endocan levels were significantly lower in AD patients with depression than in AD patients without depression or healthy controls. Serum endocan levels were negatively correlated with SGDS-K scores but not with MMSE-KC scores in AD patients.Conclusions. This study suggests that serum endocan levels might be associated with depression in AD. Future studies are needed to investigate the pathophysiological mechanisms or the role of endocan in AD with depression.

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