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 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 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 Biomarkers in Alzheimer’s disease

2021 ◽  
Author(s):  
Larissa Maria de Paula Rebouças da Costa ◽  
Gabriel de Souza Torres ◽  
Kauan Alves Sousa Madruga ◽  
Poliana Rafaela dos Santos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Low Cost ◽  
Meta Analysis ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Blood Tests ◽  
Pubmed Database ◽  
Amyloid Aβ ◽  
Phosphorylated Tau Protein

Background: Alzheimer’s disease (AD) is the most common cause of dementia and cognitive dysfunction in old ages. AD is characterised by beta- amyloid (Aβ) plaques and neurofibrillary tangles of the hyper-phosphorylated Tau protein. It has an extensive preclinical stage, which emphasizes the importance of the biological components related to an early diagnostic: biomarkers. Objectives: After critical analysis of the selected literature, this review has the goal of describing the main biomarkers in AD and discussing different ways of detecting it. Methods: This review was elaborated after a literature review in the PubMed database, with 15 articles published between 2016 and 2021. The keywords were used with the boolean operator “AND”. Articles of meta-analysis, review and systematic review were selected. Results: It was found central biomarkers for the AD diagnostic, such as Tau and Aβ. The following tests were used: CSF puncture; blood tests; neuroimaging; saliva and mucosa samples. Aβ and Tau can be collected by CSF or PET-TC. Conclusions: Biomarkers play an important role in early AD diagnostic, even with limitations in the tests. The CSF and PET-TC are expensive methods, only used in atypical cases of AD. Reliable blood tests remain in development. In conclusion, there’s the need for more studies about alternative diagnostic tests, that are non-invasive and have low cost. Those developments can be beneficial for health plans, helping early diagnosis of AD.

scholarly journals Small nucleolar RNAs in plasma and their discriminatory power as diagnostic biomarkers of Alzheimer's disease

2021 ◽  
Author(s):  
Nicholas F Fitz ◽  
Kyong Nyon Nam ◽  
Jiebiao Wang ◽  
M. Ilyas Kamboh ◽  
Radosveta Koldamova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Discriminatory Power ◽  
Diagnostic Process ◽  
Rna Seq ◽  
Diagnostic Biomarkers ◽  
Significant Enrichment ◽  
High Discriminatory Power ◽  
Nucleolar Rnas

The clinical diagnosis of Alzheimer's disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ; peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs - a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs - SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.

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 Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer’s Disease versus Age-Matched Controls: A Presymptomatic Stage Study

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Aurélie Doméné ◽  
Chelsea Cavanagh ◽  
Guylène Page ◽  
Sylvie Bodard ◽  
Christophe Klein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Transgenic Mouse Model ◽  
Astrocyte Activation ◽  
Western Blots ◽  
Cytokine Induction ◽  
Model Of Alzheimer’S Disease ◽  
Presymptomatic Stage ◽  
Gfap Expression

Recent mouse studies of the presymptomatic stage of Alzheimer’s disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFαcontributes to increased Aβproduction from the Aβprecursor protein (APP), we assessed a putative correlation between APP/Aβand TNFαduring the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβwas not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFαand APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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