scholarly journals microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 113
Author(s):  
Dolores Siedlecki-Wullich ◽  
Alfredo J. Miñano-Molina ◽  
José Rodríguez-Álvarez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Time Window ◽  
Cost Effective ◽  
Synaptic Function ◽  
Therapeutic Interventions ◽  
Synaptic Homeostasis ◽  
Diagnosis And Prognosis ◽  
Individual Mirnas ◽  
Long Time

Pathogenic processes underlying Alzheimer’s disease (AD) affect synaptic function from initial asymptomatic stages, long time before the onset of cognitive decline and neurodegeneration. Therefore, reliable biomarkers enabling early AD diagnosis and prognosis are needed to maximize the time window for therapeutic interventions. MicroRNAs (miRNAs) have recently emerged as promising cost-effective and non-invasive biomarkers for AD, since they can be readily detected in different biofluids, including cerebrospinal fluid (CSF) and blood. Moreover, a growing body of evidence indicates that miRNAs regulate synaptic homeostasis and plasticity processes, suggesting that they may be involved in early synaptic dysfunction during AD. Here, we review the current literature supporting a role of miRNAs during early synaptic deficits in AD, including recent studies evaluating their potential as AD biomarkers. Besides targeting genes related to Aβ and tau metabolism, several miRNAs also regulate synaptic-related proteins and transcription factors implicated in early synaptic deficits during AD. Furthermore, individual miRNAs and molecular signatures have been found to distinguish between prodromal AD and healthy controls. Overall, these studies highlight the relevance of considering synaptic-related miRNAs as potential biomarkers of early AD stages. However, further validation studies in large cohorts, including longitudinal studies, as well as implementation of standardized protocols, are needed to establish miRNA-based biomarkers as reliable diagnostic and prognostic tools.

scholarly journals Electroencephalography as a Non-Invasive Biomarker of Alzheimer’s Disease: A Forgotten Candidate to Substitute CSF Molecules?

2021 ◽  
Vol 22 (19) ◽  
pp. 10889
Author(s):  
Paloma Monllor ◽  
Ana Cervera-Ferri ◽  
Maria-Angeles Lloret ◽  
Daniel Esteve ◽  
Begoña Lopez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Markers ◽  
Cost Effective ◽  
Disease Diagnosis ◽  
Therapeutic Interventions ◽  
Underlying Process ◽  
Non Invasive ◽  
Diagnosis And Prognosis ◽  
Over Time

Biomarkers for disease diagnosis and prognosis are crucial in clinical practice. They should be objective and quantifiable and respond to specific therapeutic interventions. Optimal biomarkers should reflect the underlying process (pathological or not), be reproducible, widely available, and allow measurements repeatedly over time. Ideally, biomarkers should also be non-invasive and cost-effective. This review aims to focus on the usefulness and limitations of electroencephalography (EEG) in the search for Alzheimer’s disease (AD) biomarkers. The main aim of this article is to review the evolution of the most used biomarkers in AD and the need for new peripheral and, ideally, non-invasive biomarkers. The characteristics of the EEG as a possible source for biomarkers will be revised, highlighting its advantages compared to the molecular markers available so far.

scholarly journals The Value of OCT and OCTA as Potential Biomarkers for Preclinical Alzheimer’s Disease: A Review Study

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 712
Author(s):  
Inés López-Cuenca ◽  
Elena Salobrar-García ◽  
Lorena Elvira-Hurtado ◽  
José A. Fernández-Albarral ◽  
Lidia Sánchez-Puebla ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Longitudinal Studies ◽  
Positron Emission Tomography Imaging ◽  
Cost Effective ◽  
Therapeutic Interventions ◽  
Preclinical Alzheimer’S Disease ◽  
Cerebral Amyloidosis ◽  
Preclinical Ad ◽  
Positron Emission

Preclinical Alzheimer’s disease (AD) includes cognitively healthy subjects with at least one positive biomarker: reduction in cerebrospinal fluid Aβ42 or visualization of cerebral amyloidosis by positron emission tomography imaging. The use of these biomarkers is expensive, invasive, and not always possible. It has been shown that the retinal changes measured by optical coherence tomography (OCT) and OCT-angiography (OCTA) could be biomarkers of AD. Diagnosis in early stages before irreversible AD neurological damage takes place is important for the development of new therapeutic interventions. In this review, we summarize the findings of different published studies using OCT and OCTA in participants with preclinical AD. To date, there have been few studies on this topic and they are methodologically very dissimilar. Moreover, these include only two longitudinal studies. For these reasons, it would be interesting to unify the methodology, make the inclusion criteria more rigorous, and conduct longer longitudinal studies to assess the evolution of these subjects. If the results were consistent across repeated studies with the same methodology, this could provide us with insight into the value of the retinal changes observed by OCT/OCTA as potential reliable, cost-effective, and noninvasive biomarkers of preclinical AD.

Therapeutic Interventions for the Suppression of Alzheimer’s Disease: Quest for a Remedy

2015 ◽  
Vol 16 (5) ◽  
pp. 346-353 ◽  
Author(s):  
Naveed Fazili ◽  
Aabgeena Naeem ◽  
Ghulam Ashraf ◽  
Siew Gan ◽  
Mohammad Kamal
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Interventions

scholarly journals Tau and TDP-43 synergy: a novel therapeutic target for sporadic late-onset Alzheimer’s disease

GeroScience ◽  
2021 ◽  
Author(s):  
Caitlin S. Latimer ◽  
Nicole F. Liachko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Hippocampal Sclerosis ◽  
Model Organism ◽  
Amyloid Β ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Biology ◽  
Rapid Cognitive Decline

AbstractAlzheimer’s disease (AD) is traditionally defined by the presence of two types of protein aggregates in the brain: amyloid plaques comprised of the protein amyloid-β (Aβ) and neurofibrillary tangles containing the protein tau. However, a large proportion (up to 57%) of AD patients also have TDP-43 aggregates present as an additional comorbid pathology. The presence of TDP-43 aggregates in AD correlates with hippocampal sclerosis, worse brain atrophy, more severe cognitive impairment, and more rapid cognitive decline. In patients with mixed Aβ, tau, and TDP-43 pathology, TDP-43 may interact with neurodegenerative processes in AD, worsening outcomes. While considerable progress has been made to characterize TDP-43 pathology in AD and late-onset dementia, there remains a critical need for mechanistic studies to understand underlying disease biology and develop therapeutic interventions. This perspectives article reviews the current understanding of these processes from autopsy cohort studies and model organism-based research, and proposes targeting neurotoxic synergies between tau and TDP-43 as a new therapeutic strategy for AD with comorbid TDP-43 pathology.

scholarly journals The Neuronal Actions of Leptin and the Implications for Treating Alzheimer’s Disease

2021 ◽  
Vol 14 (1) ◽  
pp. 52
Author(s):  
Kirsty Hamilton ◽  
Jenni Harvey
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Hippocampal Formation ◽  
Synaptic Function ◽  
Receptor Expression ◽  
Neuroprotective Actions ◽  
Novel Target ◽  
Leptin System

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.

Measuring Disease Modification in Alzheimer's Disease

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 11-14
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunoglobulin A ◽  
Disease Process ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Modification ◽  
Amyloid Disease ◽  
Therapeutic Modalities ◽  
Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

scholarly journals Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aidan Kenny ◽  
Eva M. Jiménez-Mateos ◽  
María Ascensión Zea-Sevilla ◽  
Alberto Rábano ◽  
Pablo Gili-Manzanaro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unmet Need ◽  
Cost Effective ◽  
Specific Protein ◽  
Tear Fluid ◽  
Initiation Factor ◽  
Non Invasive ◽  
A Genome ◽  
Potential Biomarker

Abstract Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.

Non-Ceruloplasmin Copper as a Stratification Biomarker of Alzheimer’s Disease Patients: How to Measure and Use It

2021 ◽  
Vol 18 ◽  
Author(s):  
Rosanna Squitti ◽  
Mariacarla Ventriglia ◽  
Alberto Granzotto ◽  
Stefano L. Sensi ◽  
Mauro Ciro Antonio Rongioletti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Cost Effective ◽  
The Elderly ◽  
The Body ◽  
Eligibility Criterion ◽  
Growing Body ◽  
Proper Balance

: Alzheimer’s disease (AD) is a type of dementia very common in the elderly. A growing body of recent evidence has linked AD pathogenesis to copper (Cu) dysmetabolism in the body. In fact, a subset of patients affected either by AD or by its prodromal form known as Mild Cognitive Impairment (MCI) have been observed to be unable to maintain a proper balance of Cu metabolism and distribution and are characterized by the presence in their serum of increased levels of Cu not bound to ceruloplasmin (non-ceruloplasmin Cu). Since serum non-ceruloplasmin Cu is a biomark- er of Wilson's disease (WD), a well-known condition of Cu-driven toxicosis, in this review, we pro- pose that in close analogy with WD, the assessment of non-ceruloplasmin Cu levels can be exploit- ed as a cost-effective stratification and susceptibility/risk biomarker for the identification of some AD/MCI individuals. The approach can also be used as an eligibility criterion for clinical trials aim- ing at investigating Cu-related interventions against AD/MCI.

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