scholarly journals Advantages and Pitfalls in Fluid Biomarkers for Diagnosis of Alzheimer’s Disease

2020 ◽  
Vol 10 (3) ◽  
pp. 63 ◽  
Author(s):  
Syed Haris Omar ◽  
John Preddy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Process ◽  
Non Invasive ◽  
Radio Imaging ◽  
Beta Peptide ◽  
Sustained Effort ◽  
Asymptomatic Individuals ◽  
Invasive Techniques ◽  
T Tau

Alzheimer’s disease (AD) is a commonly occurring neurodegenerative disease in the advanced-age population, with a doubling of prevalence for each 5 years of age above 60 years. In the past two decades, there has been a sustained effort to find suitable biomarkers that may not only aide with the diagnosis of AD early in the disease process but also predict the onset of the disease in asymptomatic individuals. Current diagnostic evidence is supportive of some biomarker candidates isolated from cerebrospinal fluid (CSF), including amyloid beta peptide (Aβ), total tau (t-tau), and phosphorylated tau (p-tau) as being involved in the pathophysiology of AD. However, there are a few biomarkers that have been shown to be helpful, such as proteomic, inflammatory, oral, ocular and olfactory in the early detection of AD, especially in the individuals with mild cognitive impairment (MCI). To date, biomarkers are collected through invasive techniques, especially CSF from lumbar puncture; however, non-invasive (radio imaging) methods are used in practice to diagnose AD. In order to reduce invasive testing on the patients, present literature has highlighted the potential importance of biomarkers in blood to assist with diagnosing AD.

scholarly journals Diagnostic Biomarkers for Alzheimer’s Disease Using Non-Invasive Specimens

2020 ◽  
Vol 9 (6) ◽  
pp. 1673 ◽  
Author(s):  
Maria Paraskevaidi ◽  
David Allsop ◽  
Salman Karim ◽  
Francis L. Martin ◽  
StJohn Crean
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Samples ◽  
Great Promise ◽  
Non Invasive ◽  
To Come ◽  
Sampling Procedures ◽  
T Tau ◽  
Analytical Approaches

Studies in the field of Alzheimer’s disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage—before critical neurons are lost. Several studies have been investigating the use of cerebrospinal fluid (CSF) and blood as clinical samples for the detection of AD with a number of established core markers, such as amyloid beta (Aβ), total tau (T-tau) and phosphorylated tau (P-tau), being at the center of clinical research interest. The use of oral samples—including saliva and buccal mucosal cells—falls under one of the least-investigated areas in AD diagnosis. Such samples have great potential to provide a completely non-invasive alternative to current CSF and blood sampling procedures. The present work is a thorough review of the results and analytical approaches, including proteomics, metabolomics, spectroscopy and microbiome analyses that have been used for the study and detection of AD using salivary samples and buccal cells. With a few exceptions, most of the studies utilizing oral samples were performed in small cohorts, which in combination with the existence of contradictory results render it difficult to come to a definitive conclusion on the value of oral markers. Proteins such as Aβ, T-tau and P-tau, as well as small metabolites, were detected in saliva and have shown some potential as future AD diagnostics. Future large-cohort studies and standardization of sample preparation and (pre-)analytical factors are necessary to determine the use of these non-invasive samples as a diagnostic tool for AD.

scholarly journals Detection of amyloid-beta and tau in tear fluid of patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Marlies Gijs ◽  
Inez H.G.B. Ramakers ◽  
Pieter Jelle Visser ◽  
Frans R.J. Verhey ◽  
Marjo P.H. van de Waarenburg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Tear Fluid ◽  
Subjective Cognitive Decline ◽  
Amyloid Beta Peptides ◽  
Non Invasive ◽  
Beta Peptides ◽  
Dementia Patients ◽  
T Tau

Abstract Background There is growing interest in finding non-invasive alternatives to cerebrospinal fluid (CSF) that could serve as front-line diagnostics for Alzheimer’s disease (AD). In this study, we investigated AD-specific biomarkers in tear fluid.Methods Tear fluid was collected from 25 patients with subjective cognitive decline SCD), 24 patients with mild cognitive impairment (MCI), 11 dementia patients and nine controls. Amyloid-beta peptides (AB38, AB40, AB42), t-tau and p-tau levels in tear fluid were determined using multiplex immunoassays.Results Tear t-tau levels in dementia, MCI and SCD patients were higher than in HC (p = 0.002, p = 0.002 and p = 0.013, respectively). A negative correlation between AB42 and t-tau was found in both tear fluid and CSF. Levels of tear p-tau were detectable in patients but not in HC.Conclusions This study shows for the first time presence of amyloid-beta peptides (AB38, AB40, AB42), t-tau and p-tau in tear fluid.

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

scholarly journals Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 980
Author(s):  
Ka-Young Kim ◽  
Ki-Young Shin ◽  
Keun-A. Chang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Web Of Science ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Blood Biomarkers ◽  
Cell Lineages ◽  
The Central Nervous System ◽  
New Biomarkers ◽  
T Tau

Alzheimer’s disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595–2.474), total-tau (SMD = 1.224, 95% CI: 0.534–1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795–4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.

scholarly journals Potential Virus Involvement in Alzheimer’s Disease: Results from a Phase IIa Trial Evaluating Apovir, an Antiviral Drug Combination

2021 ◽  
pp. 1-19
Author(s):  
Nina Lindblom ◽  
Lars Lindquist ◽  
Jacob Westman ◽  
Mikael Åström ◽  
Roger Bullock ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Drug Combination ◽  
Antiviral Treatment ◽  
Antiviral Drug ◽  
Disease Process ◽  
Drop Out ◽  
Large Drop ◽  
Drop Out Rate

Background: Accumulating data suggest infectious agents are involved in Alzheimer’s disease (AD). The two primary aims of this trial were to assess safety and efficacy of an antiviral drug combination on AD progression. Objective: The trial evaluated whether Apovir, a combination of two antiviral agents, pleconaril (active on enteroviruses) and ribavirin (active on several viruses), could slow AD progression. Methods: Sixty-nine patients 60–85 years were treated with Apovir or placebo for 9 months and followed until 12 months after end of treatment. Cognitive tests, safety, biomarkers, drug plasma, and cerebrospinal fluid concentrations were assessed. Results: The tolerability of Apovir was compromised as demonstrated by the large drop-out rate and increased frequency and severity of adverse events. The primary endpoint, demonstrating a difference in change from baseline to 9 months between groups in ADAS-cog total score, was not met (p = 0.1809). However, there were observations indicating potential effects on both ADAS-cog and CDR-SB but these effects need to be verified. Also, there was a decrease in cerebrospinal fluid amyloid-β in Apovir at 9 months (p = 0.0330) but no change in placebo. Conclusion: This was the first randomized, placebo controlled clinical trial exploring antiviral treatment on AD progression. The trial is considered inconclusive due to the large drop-out rate. New trials are needed to verify if the indications of effect observed can be confirmed and which component(s) in Apovir contributed to such effects. Pleconaril alone may be studied to improve the tolerability and to verify if enterovirus is involved in the disease process.

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.

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