Exosome-encapsulated microRNAs as promising biomarkers for Alzheimer’s disease

2019 ◽  
Vol 31 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Jian-jiao Chen ◽  
Guang Yang ◽  
Qing-qing Yan ◽  
Jie Zhao ◽  
Shao Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Proteins ◽  
Diagnostic Biomarkers ◽  
Clinical Phase ◽  
Preclinical Phase ◽  
Cerebrospinal Fluid Biomarkers ◽  
Exosomal Mirnas ◽  
And Function ◽  
Therapeutic Prevention

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disease that locks into long clinical latency and low curative ratio. Therefore, early diagnosis before the clinical phase is quite essential and may be effective for therapeutic prevention. Peripheral blood or cerebrospinal fluid biomarkers symbolizing functional neuronal impairment are gradually applied to diagnose AD in research studies. Exosomes have generated immense interest in the diagnosis field of neurodegenerative disorders after confirmation of their roles as mediators, delivering important proteins and microRNAs (miRNAs) in intercellular communication. Compelling research results reveal that miRNAs released from exosomes modulate expression and function of amyloid precursor proteins and tau proteins. These findings open up possibility that dysfunctional exosomal miRNAs may influence AD progression. In this review, we summarized the existing knowledge of exosomal miRNAs and their involvement in AD, emphasizing their potential to serve as diagnostic biomarkers during the preclinical phase of AD.

scholarly journals Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jian-jiao Chen ◽  
Bin Zhao ◽  
Jie Zhao ◽  
Shao Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Proteins ◽  
Neural Cells ◽  
Amyloid Precursor Proteins ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
Precursor Proteins ◽  
And Function ◽  
Macromolecular Drug Delivery

Exosomes are bilipid layer-enclosed vesicles derived from endosomes and are released from neural cells. They contain a diversity of proteins, mRNAs, and microRNAs (miRNAs) that are delivered to neighboring cells and/or are transported to distant sites. miRNAs released from exosomes appear to be associated with multiple neurodegenerative conditions linking to Alzheimer’s disease (AD) which is marked by hyperphosphorylated tau proteins and accumulation of Aβ plaques. Exciting findings reveal that miRNAs released from exosomes modulate the expression and function of amyloid precursor proteins (APP) and tau proteins. These open up the possibility that dysfunctional exosomal miRNAs may influence AD progression. In addition, it has been confirmed that the interaction between miRNAs released by exosomes and Toll-like receptors (TLR) initiates inflammation. In exosome support-deprived neurons, exosomal miRNAs may regulate neuroplasticity to relieve neurological damage. In this review, we summarize the literature on the function of exosomal miRNAs in AD pathology, the potential of these miRNAs as diagnostic biomarkers in AD, and the use of exosomes in the delivery of miRNAs which may lead to major advances in the field of macromolecular drug delivery.

scholarly journals Criteria for the diagnosis of Alzheimer's disease: Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

2011 ◽  
Vol 5 (3) ◽  
pp. 146-152 ◽  
Author(s):  
Norberto Anízio Ferreira Frota ◽  
Ricardo Nitrini ◽  
Benito Pereira Damasceno ◽  
Orestes V. Forlenza ◽  
Elza Dias-Tosta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Phase ◽  
Visual Spatial ◽  
Cerebrospinal Fluid Biomarkers ◽  
Diagnosis Of Dementia ◽  
Research Criteria ◽  
Initial Forms ◽  
New Criteria ◽  
Cognitive Neurology

Abstract This consensus prepared by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology is aimed at recommending new criteria for the diagnosis of dementia and Alzheimer's disease (AD) in Brazil. A revision was performed of the proposals of clinical and of research criteria suggested by other institutions and international consensuses. The new proposal for the diagnosis of dementia does not necessarily require memory impairment if the cognitive or behavioral compromise affects at least two of the following domains: memory, executive function, speech, visual-spatial ability and change in personality. For the purpose of diagnosis, AD is divided into three phases: dementia, mild cognitive impairment and pre-clinical phase, where the latter only applies to clinical research. In the dementia picture, other initial forms were accepted which do not involve amnesia and require a neuroimaging examination. Cerebrospinal fluid biomarkers are recommended for study, but can be utilized as optional instruments, when deemed appropriate by the clinician.

Recent progress towards vaccines and antibody-based therapies against Alzheimer's disease

2021 ◽  
Vol 21 ◽  
Author(s):  
Wenbo Ji ◽  
Baofeng Gong ◽  
Hong Jin ◽  
Xiaohan Chen ◽  
Peng Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Phase 1 ◽  
Amyloid Β ◽  
Communication Disorders ◽  
Tau Proteins ◽  
Research Progress ◽  
Term Survival ◽  
Clinical Phase

: Alzheimer's disease (AD), one of the progressive neurodegenerative disorders, is featured by clinical features such as memory loss, acquired skill loss, apraxia, and interpersonal and social communication disorders. The AD hallmarks at neuropathological level include intracellular neurofibrillary tangles constituted by the hyperphosphorylated tau protein as well as the senile extracellular plaques dominated by the amyloid-β (Aβ) deposits. At present, AD treatment is mainly targeted towards improving symptoms, and effective drugs to delay or stop disease progression are lacking. vaccines and antibody-based therapies are a type of natural, synthetic, and gene recombinant biological product that treat or prevent disease progression by stimulating specific or non-specific immune responses. Compared with traditional targeted drugs, vaccines and antibody-based therapies have better safety and effectiveness, and can even maintain the expression and stability of Aβ and Tau proteins in patients for a long time. Logically, vaccines and antibody-based therapies are somewhat different from traditional drugs because these drugs can achieve the therapeutic effect of AD by activating immune cells and regulating the immune system of patients themselves, thereby clearing disease-related proteins, and long-term survival or even complete cure is observed in some patients after receiving the immunotherapy. Currently available vaccines and antibody-based therapies mainly target Aβ and phosphorylated tau proteins. There are 44 vaccines and antibody-based therapies for AD, among which nine drugs are discontinued, three drugs are inactive, eleven drugs are in clinical phase 1, twelve drugs are in clinical phase 2, and seven drugs are in clinical phase 3. Currently, no vaccines and antibody-based therapies have been approved for AD treatment. In this paper, we review and analyse the research progress of vaccines and antibody-based therapies that are used to treat AD.

Neuroimaging and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease

2017 ◽  
Author(s):  
Brian A. Gordon ◽  
Stephanie J.B. Vos ◽  
Anne M. Fagan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Amyloid Plaques ◽  
Blood Tests ◽  
Preclinical Phase ◽  
Disease Modifying Therapies ◽  
Cerebrospinal Fluid Biomarkers ◽  
Neuroimaging Techniques

Alzheimer’s disease is characterized by a long asymptomatic (preclinical) phase during which disease-related pathology accumulates in the absence of overt cognitive symptoms. The most prominent neuropathologies are extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Until recently such pathology was observable only at autopsy. Now these, and other novel pathological markers, can be measured in living individuals using cerebrospinal fluid assays, blood tests, and neuroimaging techniques to track disease progression. Understanding changes in these biomarkers is critical for diagnosis, monitoring disease progression, and for the development of disease-modifying therapies. This chapter reviews the current scientific understanding regarding the use of biomarkers to assess Alzheimer’s disease pathology.

scholarly journals Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

2021 ◽  
pp. 1-11
Author(s):  
Danni Li ◽  
Lin Zhang ◽  
Nathaniel W. Nelson ◽  
Michelle M. Mielke ◽  
Fang Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Daily Living ◽  
Short Term ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Linear Mixed Effects ◽  
Future Studies ◽  
Rate Of Decline ◽  
And Function

Background: Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown. Objective: To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial. Methods: Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes. Results: Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082). Conclusion: This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

scholarly journals Resting State Alpha Electroencephalographic Rhythms Are Differently Related to Aging in Cognitively Unimpaired Seniors and Patients with Alzheimer’s Disease and Amnesic Mild Cognitive Impairment

2021 ◽  
pp. 1-30
Author(s):  
Claudio Babiloni ◽  
Raffaele Ferri ◽  
Giuseppe Noce ◽  
Roberta Lizio ◽  
Susanna Lopez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Resting State ◽  
Diagnostic Biomarkers ◽  
Eyes Closed ◽  
Topographical Effects ◽  
And Gender ◽  
International Archive

Background: In relaxed adults, staying in quiet wakefulness at eyes closed is related to the so-called resting state electroencephalographic (rsEEG) rhythms, showing the highest amplitude in posterior areas at alpha frequencies (8–13 Hz). Objective: Here we tested the hypothesis that age may affect rsEEG alpha (8–12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI). Methods: Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals (matched for demography, education, and gender) were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14–30 Hz) and gamma (30–40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles). Results: As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. On the contrary, in relation to the younger ADMCI subgroups, the older one displayed a lesser reduction in those rhythms. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions revealed by neuroimaging, and clinical and neuropsychological scores. Conclusion: The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier versus later onset of the AD.

scholarly journals Unique Sleep and Circadian Rhythm Dysfunction Neuroinflammatory and Immune Profiles in Alzheimer’s Disease with Mild Cognitive Impairment

2021 ◽  
pp. 1-6
Author(s):  
Jagan A. Pillai ◽  
James Bena ◽  
Lynn M. Bekris ◽  
Nancy Foldvary-Schaefer ◽  
Catherine Heinzinger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Circadian Rhythm ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cerebrospinal Fluid Biomarkers ◽  
Circulating Markers

Sleep dysfunction has been identified in the pathophysiology of Alzheimer’s disease (AD); however, the role and mechanism of circadian rhythm dysfunction is less well understood. In a well-characterized cohort of patients with AD at the mild cognitive impairment stage (MCI-AD), we identify that circadian rhythm irregularities were accompanied by altered humoral immune responses detected in both the cerebrospinal fluid and plasma as well as alterations of cerebrospinal fluid biomarkers of neurodegeneration. On the other hand, sleep disruption was more so associated with abnormalities in circulating markers of immunity and inflammation and decrements in cognition.

scholarly journals Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 957
Author(s):  
Brad T. Casali ◽  
Erin G. Reed-Geaghan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cells ◽  
Expression Patterns ◽  
Brain Parenchyma ◽  
Primary Role ◽  
And Function ◽  
Inflammatory Milieu ◽  
The Brain ◽  
Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

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