How useful are biomarkers for the diagnosis of Alzheimer's disease and especially for its therapy?
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ABSTRACT:
SUBMITTER: Valenza M
PROVIDER: S-EPMC9083181 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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How useful are biomarkers for the diagnosis of Alzheimer's disease and especially for its therapy?
Valenza Marta M Scuderi Caterina C
Neural regeneration research 20221001 10
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Project description:An accurate and early diagnosis of Alzheimer's disease (AD) is important to select optimal patient care and is critical in current clinical trials targeting core AD neuropathological features. The past decades, much progress has been made in the development and validation of cerebrospinal fluid (CSF) biomarkers for the biochemical diagnosis of AD, including standardization and harmonization of (pre-) analytical procedures. This has resulted in three core CSF biomarkers for AD diagnostics, namely the 42 amino acid long amyloid-beta peptide (A?1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181). These biomarkers have been incorporated into research diagnostic criteria for AD and have an added value in the (differential) diagnosis of AD and related disorders, including mixed pathologies, atypical presentations, and in case of ambiguous clinical dementia diagnoses. The implementation of the CSF A?1-42/A?1-40 ratio in the core biomarker panel will improve the biomarker analytical variability, and will also improve early and differential AD diagnosis through a more accurate reflection of pathology. Numerous biomarkers are being investigated for their added value to the core AD biomarkers, aiming at the AD core pathological features like the amyloid mismetabolism, tau pathology, or synaptic or neuronal degeneration. Others aim at non-AD neurodegenerative, vascular or inflammatory hallmarks. Biomarkers are essential for an accurate identification of preclinical AD in the context of clinical trials with potentially disease-modifying drugs. Therefore, a biomarker-based early diagnosis of AD offers great opportunities for preventive treatment development in the near future.
| S-EPMC5870045 | biostudies-other
Project description:Many factors are involved in Alzheimer's disease (AD) pathology including tau phosphorylation, amyloid β protein (Aβ) accumulation, lipid dysregulation, oxidative stress, and inflammation. The markers of these pathological processes in cerebral spinal fluid are used currently for AD diagnosis. However, peripheral biomarkers are the need of the hour for large population screening for AD. The main objective of the present study is to evaluate the peripheral levels of redox markers, lipid peroxidation (LPO) indicators, and pathological markers in AD patients. Blood was collected from AD patients (n = 45), controls (n = 45), and analyzed for pathological markers of AD including Aβ42 and tau, LPO, and redox indicators. Plasma Aβ42 was significantly (P < 0.001) elevated while total tau was decreased in AD compared to controls. Hydroxynonenal (HNE) and malondialdehyde (MDA) were higher (P < 0.001) in AD patients pointing the enhanced LPO in AD pathology. Receiver operating characteristic curve (ROC) analysis indicated that HNE is a better indicator of LPO compared to MDA. Plasma glutathione (GSH) level was significantly (P < 0.001) low while oxidized glutathione (GSSG) level was higher (P < 0.001) in AD patients with corresponding decrease in GSH/GSSG ratio (P < 0.001). ROC analysis indicated that GSH/GSSG ratio can be used as reliable indicator for redox imbalance in AD with a cutoff value of <8.73 (sensitivity 91.1%, specificity 97.8%). Correlation analysis revealed a positive correlation for both HNE and MDA with Aβ42 and a negative correlation with total tau. Negative correlation was observed between GSH/GSSG ratio and LPO markers. While oxidative stress has been implicated in pathology of various neurodegenerative disorders, the present study pinpoints the direct link between LPO and Aβ production in plasma of AD patients. Normally, at low amyloid concentration in body fluids, this peptide shown to function as a strong metal chelating antioxidant. However, when the Aβ production enhanced as in AD, through gain of functional transformation, Aβ evolves into prooxidant, thereby enhancing oxidative stress and LPO. Altered redox status with enhanced LPO observed in AD blood could contribute to the oxidation and S-glutathionylation proteins, which has to be addressed in future studies.
| S-EPMC5509803 | biostudies-other
Project description:Alzheimer's disease (AD) is a complex neurodegenerative disease that requires extremely specific biomarkers for its diagnosis. For current diagnostics capable of identifying AD, the development and validation of early stage biomarkers is a top research priority. Body-fluid biomarkers might closely reflect synaptic dysfunction in the brain and, thereby, could contribute to improving diagnostic accuracy and monitoring disease progression, and serve as markers for assessing the response to disease-modifying therapies at early onset. Here, we highlight current advances in the research on the capabilities of body-fluid biomarkers and their role in AD pathology. Then, we describe and discuss current applications of the potential biomarkers in clinical diagnostics in AD.
| S-EPMC7277970 | biostudies-literature
Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment and dementia in older individuals throughout the world. The main hallmarks of AD include brain atrophy, extracellular deposition of insoluble amyloid-β (Aβ) plaques, and the intracellular aggregation of protein tau in neurofibrillary tangles. These pathological modifications start many years prior to clinical manifestations of disease and the spectrum of AD progresses along a continuum from preclinical to clinical phases. Therefore, identifying specific biomarkers for detecting AD at early stages greatly improves clinical management. However, stable and non-invasive biomarkers are not currently available for the early detection of the disease. In the search for more reliable biomarkers, epigenetic mechanisms, able to mediate the interaction between the genome and the environment, are emerging as important players in AD pathogenesis. Herein, we discuss altered epigenetic signatures in blood as potential peripheral biomarkers for the early detection of AD in order to help diagnosis and improve therapy.
| S-EPMC9332601 | biostudies-literature
Project description:Alzheimer's disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support. AD is a multifactorial disease, and knowing its underlying pathological mechanisms is crucial to propose new and valuable biomarkers. In this review, we summarize some of the main biomarkers described in AD, which have been evaluated mainly by imaging studies in cerebrospinal fluid and blood samples. Furthermore, we describe and propose neuronal precursors derived from the olfactory neuroepithelium as a potential resource to evaluate some of the widely known biomarkers of AD and to gear toward searching for new biomarkers. These neuronal lineage cells, which can be obtained directly from patients through a non-invasive and outpatient procedure, display several characteristics that validate them as a surrogate model to study the central nervous system, allowing the analysis of AD pathophysiological processes. Moreover, the ease of obtaining and harvesting endows them as an accessible and powerful resource to evaluate biomarkers in clinical practice.
| S-EPMC10813897 | biostudies-literature
Project description:Alzheimer's Disease (AD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 50 AD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of AD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Parkinson's disease and breast cancer, respectively) confirmed their specificity.
2011-07-12 | E-GEOD-29676 | biostudies-arrayexpress
Project description:Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.
| S-EPMC11564087 | biostudies-literature
Project description:Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis. We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD. We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD. In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls. Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.
| S-EPMC7963160 | biostudies-literature
Project description:Beta amyloid peptide, tau, and phosphorylated tau are well recognized as promising biomarkers for the diagnosis of Alzheimer's disease (AD). In this work, we developed a direct, versatile, and ultrasensitive multiplex assay for the quantification of trace amounts of these protein biomarkers for AD in different types of biological fluids including cerebrospinal fluid, serum, saliva, and urine. The detection assay is based on the immunoreaction between the target proteins and their corresponding pair of antibodies followed by fluorescence labelling with a newly developed indolium-based turn-on fluorophore, namely SIM. SIM was tailor-made as a reporter to provide a high signal-to-noise ratio for the detection assay. An exceptionally low limit of detection down to the femto-molar level was achieved in this assay with minute consumption of the sample. This versatile detection assay is capable of reliably quantifying not only the target proteins simultaneously from a CSF sample in an hour but also trace amounts of protein biomarkers in saliva and urine. This assay has a high potential to serve as a practical tool for the diagnosis of AD.
| S-EPMC6094176 | biostudies-literature
Project description:Alzheimer's Disease (AD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators.
2011-07-13 | GSE29676 | GEO