Alzheimer’s disease (AD) is one of the most frequent neurodegenerative diseases affecting more than 35 million people in the world, and its incidence is estimated to triple by 2050. Alzheimer’s disease is an age-related disease characterized by the progressive loss of memory and cognitive function, caused by the unstoppable neurodegeneration and brain atrophy. Current AD treatments only relieve the symptoms. The first molecular signs of the disease identified decades ago and were related to the tau neurofibrillary tangles and the β amyloid plaques. Despite the considerable progress in the diagnostic field, there is no certain knowledge of the specific biomarkers reflecting molecular mechanisms that trigger the symptoms of the disease. Therefore, there is an enormous need to find biomarkers useful for early diagnosis, before the first symptoms appear, and develop new therapeutic targets, which would guarantee improving patients’ quality of life. Researchers from all around the world are looking for biomarkers that can be identified in different biological fluids such as plasma, serum, and cerebrospinal fluid, specific for Alzheimer’s disease. In this review, we would like to resume some of the most interesting discovery in pathological mechanisms underlying Alzheimer’s disease and promising biomarkers.
Background: Lipid metabolism-related biomarkers gain increasing researchers interest in the field of neurodegenerative disorders. Mounting evidence have indicated the role of fatty acid-binding proteins and pathology lipid metabolism in Alzheimer’s Disease (AD). The imbalance of fatty acids (FA) and lipids may negatively affect brain functions related to neurodegenerative disorders. The ApoE4 and FABP3 proteins may reflect processes leading to neurodegeneration. This study aimed to evaluate the relationship between the CSF levels of FABP3 and ApoE4 proteins and cognitive decline as well as the diagnostic performance of these candidate biomarkers in AD and mild cognitive impairment (MCI). Methods: A total of 70 subjects, including patients with AD, MCI, and non-demented controls, were enrolled in the study. CSF concentrations of FABP3 and ApoE4 were measured using immunoassay technology. Results: Significantly higher CSF concentrations of FABP3 and ApoE4 were observed in AD patients compared to MCI subjects and individuals without cognitive impairment. Both proteins were inversely associated with Aβ42/40 ratio: ApoE4 (rho = −0.472, p < 0.001), and FABP3 (rho = −0.488, p < 0.001) in the whole study group, respectively. Additionally, FABP3 was negatively correlated with Mini-Mental State Examination score in the whole study cohort (rho = −0.585 p < 0.001). Conclusion: Presented results indicate the pivotal role of FABP3 and ApoE4 in AD pathology as lipid-related biomarkers, but studies on larger cohorts are needed.
Alzheimer’s disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer’s Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.
Neurogranin (Ng) and visinin-like protein 1 (VILIP-1) are promising candidates for Alzheimer’s Disease (AD) biomarkers closely related to synaptic and neuronal degeneration. Both proteins are involved in calcium-mediated pathways. The meta-analysis was performed in random effects based on the ratio of means (RoM) with calculated pooled effect size. The diagnostic utility of these proteins was examined in cerebrospinal fluid (CSF) of patients in different stages of AD compared to control (CTRL). Ng concentration was also checked in various groups with positive (+) and negative (-) amyloid beta (Aβ). Ng highest levels of RoM were observed in the AD (n = 1894) compared to CTRL (n = 2051) group (RoM: 1.62). Similarly, the VILIP-1 highest values of RoM were detected in the AD (n = 706) compared to CTRL (n = 862) group (RoM: 1.34). Concentrations of both proteins increased in more advanced stages of AD. However, Ng seems to be an earlier biomarker for the assessment of cognitive impairment. Ng appears to be related with amyloid beta, and the highest levels of Ng in CSF was observed in the group with pathological Aβ+ status. Our meta-analysis confirms that Ng and VILIP-1 can be useful CSF biomarkers in differential diagnosis and monitoring progression of cognitive decline. Although, an additional advantage of the protein concentration Ng is the possibility of using it to predict the risk of developing cognitive impairment in normal controls with pathological levels of Aβ1-42. Analyses in larger cohorts are needed, particularly concerning Aβ status.
Colorectal cancer (CRC) is one of the most frequently diagnosed neoplasms. Despite the advances in diagnostic tools and treatments, the number of CRC cases is increasing. Therefore, it is vital to search for new parameters that could be useful in its diagnosis. Thus, we wanted to assess the usefulness of selected CC chemokines (CCL2, CCL4, and CCL15) in CRC. The study included 115 subjects (75 CRC patients and 40 healthy volunteers). The serum concentrations of all parameters were measured using a multiplexing method (Luminex). The CRP levels were determined by immunoturbidimetry, and the classical tumor markers (CEA and CA 19-9) were measured using CMIA (chemiluminescent microparticle immunoassay). The concentrations of all parameters were higher in the CRC group when compared to the healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of all estimated CC chemokines were higher than those of CA 19-9. Interestingly, the obtained results also suggest CCL2’s significance in the determination of local metastases and CCL4’s significance in the determination of distant metastases. However, further studies concerning the role of selected CC chemokines in the course of colorectal cancer are necessary to confirm and to fully clarify their diagnostic utility and their clinical application as markers of CRC development.
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