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 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.

Performance of Validated MicroRNA Biomarkers for Alzheimer’s Disease in Mild Cognitive Impairment

2020 ◽  
Vol 78 (1) ◽  
pp. 245-263
Author(s):  
Ursula S. Sandau ◽  
Jack T. Wiedrick ◽  
Sierra J. Smith ◽  
Trevor J. McFarland ◽  
Theresa A. Lusardi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Stage ◽  
Linear Trend ◽  
Area Under The Curve ◽  
Classification Performance ◽  
T Tau ◽  
Median Expression

Background: Cerebrospinal fluid (CSF) microRNA (miRNA) biomarkers of Alzheimer’s disease (AD) have been identified, but have not been evaluated in prodromal AD, including mild cognitive impairment (MCI). Objective: To assess whether a set of validated AD miRNA biomarkers in CSF are also sensitive to early-stage pathology as exemplified by MCI diagnosis. Methods: We measured the expression of 17 miRNA biomarkers for AD in CSF samples from AD, MCI, and cognitively normal controls (NC). We then examined classification performance of the miRNAs individually and in combination. For each miRNA, we assessed median expression in each diagnostic group and classified markers as trending linearly, nonlinearly, or lacking any trend across the three groups. For trending miRNAs, we assessed multimarker classification performance alone and in combination with apolipoprotein E ɛ4 allele (APOE ɛ4) genotype and amyloid-β42 to total tau ratio (Aβ42:T-Tau). We identified predicted targets of trending miRNAs using pathway analysis. Results: Five miRNAs showed a linear trend of decreasing median expression across the ordered diagnoses (control to MCI to AD). The trending miRNAs jointly predicted AD with area under the curve (AUC) of 0.770, and MCI with AUC of 0.705. Aβ42:T-Tau alone predicted MCI with AUC of 0.758 and the AUC improved to 0.813 (p = 0.051) after adding the trending miRNAs. Multivariate correlation of the five trending miRNAs with Aβ42:T-Tau was weak. Conclusion: Selected miRNAs combined with Aβ42:T-Tau improved classification performance (relative to protein biomarkers alone) for MCI, despite a weak correlation with Aβ42:T-Tau. Together these data suggest that that these miRNAs carry novel information relevant to AD, even at the MCI stage. Preliminary target prediction analysis suggests novel roles for these biomarkers.

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

2021 ◽  
Vol 3 (1) ◽  
pp. 12-18
Author(s):  
Shyamasri Biswas ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Success ◽  
Potential Game ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Presymptomatic Stage ◽  
The Subject ◽  
Made In

The emergence of biomarkers in biologic fluids is considered an important milestone in the field of Alzheimer’s disease (AD) research. Biomarkers are widely considered critically important for the diagnosis and therapeutic intervention of the disease. It is believed that an early diagnosis of AD at a presymptomatic stage could provide the key for a successful intervention and treatment of AD. It is due to the reason that preventative and therapeutic strategies that are known to be AD stage-dependent can have a better chance of clinical success at a very early stage of the disease when critical neurons are not lost. To this end, current clinical trials are extensively being employed by taking advantage of different diagnostic biomarkers. While there has been notable progress in biomarkers for AD, the current research emphasis has been on exploring non-invasive biomarkers due to the advantages of cost-effectiveness, rapid diagnosis and significantly less medical procedural complexities that make these biomarkers potential game changer in AD diagnostics. Here, we present a bird eye view on the subject and discuss the progress made in important non-invasive biomarkers for AD.

scholarly journals Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

2014 ◽  
Vol 10 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Kirsten L. Viola ◽  
James Sbarboro ◽  
Ruchi Sureka ◽  
Mrinmoy De ◽  
Maíra A. Bicca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Imaging ◽  
Early Stage ◽  
Non Invasive

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 Plasma Biomarkers Ascertained With Immunomagnetic Reduction Diagnosing Early-Stage Alzheimer's Disease: A Systematic Review

2020 ◽  
Author(s):  
Pui-Un Tang ◽  
I-Hsieh Wu ◽  
Ian-Hou Lao ◽  
Wai Leong ◽  
Chaur-Jong Hu
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Final Analysis ◽  
Public Health Issue ◽  
Healthy Population ◽  
Control Groups ◽  
Ageing Society ◽  
T Tau

ABSTRACT Introduction Alzheimer's disease (AD) will become a prominent public health issue in the future given its cognitively debilitating nature. As the advent of global ageing society is expected, AD may bring tremendous socioeconomical costs if current diagnosis methods stay put. In this article, we performed a systematic review of a recent (less than 10 years) ultrasensitive technology, the immunomagnetic reduction (IMR), which shows promising potential of early diagnosis of AD. Methods We searched the Pubmed and Embase databases for studies that included keywords “early-stage Alzheimer's disease” and “immunomagnetic signal reduction.” Results After full-text review, a total of 7 studies were included for final analysis. Most included studies have reported on Aβ40, Aβ42, t-tau, and levels of these biomarkers in the plasma of early AD patients comparing those in the healthy population. The ranges of the mean Aβ40 levels are as follows: 59.2 to 60.9 for control groups and 36.9 to 39.5 pg/mL for AD. Aβ42 and t-tau concentrations are both markedly lower than Aβ40, Aβ42 at 15.5 to 16.1 for control groups and 17.9 to 19 pg/mL for AD; t-tau levels were 13.5 to 14.3 for control groups and 39.4 to 46.7 pg/mL for AD. There is a significant increasing level of plasma Aβ42 by IMR assays in early AD patients across nearly all the included studies. There is a possible relationship between plasma levels of IMR AD biomarkers and (1) degree of hippocampal atrophy using magnetic resonance imaging, and (2) amount of brain amyloid accumulation using positron emission tomography. Conclusion IMR assay is an ultrasensitivity technique that is useful for detection of early AD, which can provide benefits on understanding the disease progression of AD and encourage early medical invention for AD patients.

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.

scholarly journals Early functional and cognitive declines measured by auditory evoked cortical potentials in Alzheimer's disease mice

2021 ◽  
Author(s):  
Ling Mei ◽  
Li-Men Liu ◽  
Kaitian Chen ◽  
Hong-Bo Zhao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Auditory Cortex ◽  
Early Stage ◽  
Cognitive Activity ◽  
Event Related Potential ◽  
Neural Activation ◽  
Non Invasive ◽  
Auditory Dysfunction ◽  
Detection And Diagnosis

Alzheimer's disease (AD) is characterized with a progressive loss of memory and cognitive decline. Early detection of AD is critical for prevention and intervention of this common neurodegenerative disease. Previous studies demonstrated that auditory dysfunction could occur at the early stage of AD. Auditory evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex but also cognitive activity in the brain. In this study, we recorded AECP in AD mice. AECP in mice usually possessed 3 waveforms. The early sensory P1 and P2 peaks were clearly visible in 1 month old mice. However, the later cognitive P3 peak was not well-developed until the age of 3 months old. In APP/PS1 AD mice, P1 and P2 were reduced at young ages (<6 months old), prior to occurrence of AD phenotypes. Different from normal aging, the cognitive peak of P3 in AD mice was diminished invisible after 4 months old. The latencies of peak N1, P2, and N2 in AD mice before 3 months were shorter than those in WT mice. Consistent with AECP changes, expression of amyloid precursor protein (APP) was visible in the AD mouse auditory cortex at 2 months old. These data indicate that AECP has significant changes in young AD mice and can serve as an early, non-invasive, objective biomarker in AD and AD-related dementia detection and diagnosis.

scholarly journals Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

2021 ◽  
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Early Stage ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Preclinical Ad ◽  
T Tau

Abstract Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β 1-42 (Aβ 1-42 ), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential. Methods: We measured NFL and Aβ 1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum. Results: With disease progression, concentrations of NFL increased, and those of Aβ 1-42 were decreases. The plasma and CSF values of NFL/Aβ 1-42 were strongly correlated ( r = 0.558). In addition, the plasma value of NFL/Aβ 1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ 1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ 1-42 changed more rapidly than did either the t-Tau or the p-Tau 181 values measured in the CSF. Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ 1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

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