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Alzheimer's disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer's disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer's disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer's disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer's disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer's disease worldwide. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia is a complex disease involving massive death of brain cells in full-term newborns. The most impressive consequence of perinatal asphyxia is a neurodegenerative brain injury called hypoxic–ischemic encephalopathy. Management of newborns after perinatal asphyxia is very difficult due to the lack of measurable biomarkers that would be able to assess the severity of the brain injury in the future, help in the selection of therapy, assess the results of treatment and determine the prognosis for the future. Thus, these limitations make long-term neurodevelopmental outcomes unpredictable during life. Quantifying biomarkers that can detect subclinical changes at a stage where routine brain monitoring or imaging is still mute would be a major advance in the care of neonates with brain neurodegeneration after asphyxia. Understanding the effect of perinatal asphyxia on changes in blood neurodegenerative biomarkers over time, which would be commonly used to assess the severity of postpartum encephalopathy, would be an important step in developing precision in predicting the consequences of brain injuries. We urgently need more accurate early predictive markers to guide clinicians when to use neuroprotective therapy. The needed neurodegenerative biomarkers may represent neuronal pathological changes that can be recognized by new technologies such as genomic and proteomic. Nevertheless, the simultaneous blood tau protein and various amyloid changes with the addition of an autophagy marker beclin 1 after perinatal asphyxia have not been studied. We decided to evaluate serum biomarkers of neuronal injury characteristic for Alzheimer's disease such as amyloid peptides (1-38, 1-40 and 1-42), tau protein and beclin 1, which can predict the progression of brain neurodegeneration in future. In this paper, we report for the first time the significant changes in the above molecules in the blood after asphyxia compared to healthy controls during the 1–7, 8–14 and 15+ days ELISA test. [ABSTRACT FROM AUTHOR]

Neurons are basic units of our nervous system used for communication between the brain and the body. Any disruption in their structures or communication can result in several disorders like Dementia and Alzheimer's disease (A.D.). In this paper, we explore the alterations in neurons causing A.D. Due to specific genetic mutations, neurons release and accumulate tau protein and beta-amyloid protein, thus hampering the communication process, leading to neuron death known as brain atrophy, and eventually shrinking the brain is the case in A.D. This paper discusses neuron modeling of a typical neuron and an Alzheimer's neuron to understand the difference and progression of A.D. and the fact that once these equations are concluded, they could be used to control the brain through a brain-computer interface. Modeling of neurons enables exploring different parameters and understanding the behavior of a particular system, and finally, concluding to represent a biological activity mathematically. [ABSTRACT FROM AUTHOR]

Introduction: Dementia is a group of disorders that causes dysfunctions in human cognitive and operating functions. Currently, it is not possible to conduct a fast, low-invasive dementia diagnostic process with the use of peripheral blood biomarkers, however, there is a great deal of research in progress covering this subject. Research on dementia biomarkers in serum validates anticipated health and economic benefits from early screening tests. Biomarkers are also essential for improving the process of developing new drugs. Methods: The result analysis, of current studies on selected biomarker concentrations (Aβ40, Aβ42, t-tau, and YKL-40) and their combination in the serum of patients with dementia and mild cognitive disorders, involved a search for papers available in Medline, PubMed, and Web of Science databases published from 2000 to 2020. Results: The results of conducted cross-sectional studies comparing Aβ40, Aβ42, and Aβ42/Aβ40 among people with cognitive disorders and a control group are incoherent. Most of the analyzed papers showed an increase in t-tau concentration in diagnosed Alzheimer's disease (AD) patients' serum, whereas results of mild cognitive impairment (MCI) groups did not differ from the control groups. In several papers on the concentration of YKL-40 and t-tau/Aβ42 ratio, the results were promising. To date, several studies have only covered the field of biomarker concentrations in dementia disorders other than AD. Conclusions: Insufficient amyloid marker test repeatability may result either from imperfection of the used laboratorial techniques or inadequate selection of control groups with their comorbidities. On the basis of current knowledge, t-tau, t-tau/Aβ42, and YKL-40 seem to be promising candidates as biomarkers of cognitive disorders in serum. YKL-40 seems to be a more useful biomarker in early MCI diagnostics, whereas t-tau can be used as a marker of progress of prodromal states in mild AD. Due to the insignificant number of studies conducted to date among patients with dementia disorders other than AD, it is not possible to make a sound assessment of their usefulness in dementia differential diagnostics. [ABSTRACT FROM AUTHOR]

Human Tau protein is the most reliable biomarker for the prediction of Alzheimer's disease (AD). However, the assay to detect low concentrations of tau protein in serum is a great challenge for the early diagnosis of AD. This paper reports an electrochemiluminescence (ECL) immunosensor for Tau protein in serum samples. Gold nanostars (AuNSs) decorated on carbon nitride nanosheets (AuNS@g-CN nanostructure) show highly strong and stable ECL activity compared to pristine CN nanosheets due to the electrocatalytic and surface plasmon effects of AuNSs. As a result of the strong electromagnetic field at branches, AuNSs showed a better ECL enhancement effect than their spherical counterpart. For the fabrication of a specific immunosensor, immobilized AuNSs were functionalized with a monoclonal antibody specific for Tau protein. In the presence of Tau protein, the ECL intensity of the immunosensor decreased considerably. Under the optimal conditions, this ECL based immunosensor exhibits a dynamic linear range from 0.1 to 100 ng mL−1 with a low limit of detection of 0.034 ng mL−1. The LOD is less than the Tau level in human serum; thus, this study provides a useful method for the determination of Tau. The fabricated ECL immunosensor was successfully applied to the detection of Tau, the biomarker in serum samples. Therefore, the present approach is very promising for application in diagnosing AD within the early stages of the disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and the associated neurodegenerative dementia have become of increasing concern in healthcare. The tau protein has been considered a key hallmark of progressive neurodegeneration. In this paper, a large-scale analysis of five datasets (more than 2500 people) from the Global Alzheimer's Association Interactive Network (GAAIN) databases was performed to investigate the association between the level of tau protein, including total tau and phosphorylated tau (p-tau), in cerebrospinal fluid (CSF) and cognitive status. Statistically significant (or marginally significant) high total tau or p-tau concentrations in CSF were observed in dementia patients compared with healthy people in all datasets. There is also a statistically significant (or marginally significant) negative correlation between p-tau concentrations in CSF and Folstein Mini-Mental State Examination (MMSE) scores. In addition, transcriptomic data derived from mouse microglial cells showed multiple genes upregulated in Toll-like receptor signaling and Alzheimer's disease pathways, including TNF, TLR2, IL-1β, and COX subunits, suggesting that the mechanism of action that relates p-tau and MMSE scores may be through overactivation of pro-inflammatory microglial activity by Aβ peptides, TNF-mediated hyperphosphorylation of tau, and the infectious spread of pathological tau across healthy neurons. Our results not only confirmed the association between tau protein level and cognitive status in a large population but also provided useful information for the understanding of the role of tau in neurodegeneration and the development of dementia. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for 70% of all dementia. Early stage diagnosis of AD is essential as there is no certain treatment after the lesion has progressed in the late stage. Nevertheless, there are still limitations of early diagnosis of AD using neuroimaging and psychological memory assessments. Here, we demonstrate ultrasensitive and multiplexed detection of pivotal AD biomarkers (Aβ 1-42 and t-Tau) in biofluids using a reduced graphene oxide field-effect transistor (gFET). The proposed approach provides a wide logarithmically linear range of detection from 10−1–105 pg mL−1 and a femtomolar-level limit of detection in biofluids (human plasma and artificial cerebrospinal fluid) as well as phosphate-buffered saline (PBS). Furthermore, as these core biomarkers have different surface charges in physiological conditions based on the isoelectric point (pI), we achieved a distinctive output signal for each biomarker. The gFET biosensor platform presented in this paper has great potential and can be used for early diagnosis of AD in clinical practice as well as accurate analysis based on the surface charge of the analytes. • The amyloid-β (Aβ) and tau protein in biofluids are pivotal biomarkers for the early stage diagnosis of Alzheimer's disease. • A graphene-based field-effect transistor (gFET) is designed for multiplexed detection of Aβ 1-42 and total tau (t-Tau). • Aβ 1-42 and t-Tau possess different charges owing to their isoelectric point, resulting in distinctive doping effects on gFET. • Femtomolar detection of Aβ 1-42 and total tau (t-Tau) have been achieved in human plasma and artificial cerebrospinal fluid. [ABSTRACT FROM AUTHOR]