Advancing Neurology through Molecular Biomarkers: Improving Insight and Therapy for Alzheimer

Francesca Prost^*
*Correspondence: Francesca Prost, Department of Neurology, University of Duisburg-Essen, 45147 Essen, Germany, Email:

Keywords

Molecular biomarkers • Neurology • Brain disorders

Introduction

Alzheimer's disease is one of the most researched areas for molecular biomarkers. Amyloid-beta (Aβ) plaques and tau protein tangles are hallmark features of AD. The levels of Aβ42, total tau and phosphorylated tau in CSF are established biomarkers that aid in the early diagnosis and monitoring of disease progression. Additionally, plasma biomarkers such as Aβ42/40 ratio and Phosphorylated Tau (p-tau181) are emerging as non-invasive diagnostic tools. Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss and behavioural changes. It is the most common cause of dementia, affecting millions of people worldwide. The complexity of AD has made it a challenging disease to diagnose and treat. However, the advent of molecular biomarkers has revolutionized the field, providing new avenues for early detection, monitoring disease progression and developing targeted therapies.

Amyloid-beta is a peptide that aggregates to form plaques in the brains of Alzheimer's patients. The imbalance between the production and clearance of Aβ is a central event in AD pathogenesis. Tau is a microtubule-associated protein that stabilizes neuronal cytoskeleton. In AD, tau becomes hyper phosphorylated, leading to the formation of neurofibrillary tangles. Neurofilament light chain is a structural protein released into the CSF and blood following neuronal injury. Elevated NfL levels are indicative of neurodegeneration and correlate with disease progression in AD [1,2]. Molecular biomarkers pave the way for personalized medicine in AD, allowing treatments to be tailored to the individual patient based on their specific biomarker profile. Molecular biomarkers have transformed our understanding of Alzheimer's disease, offering new possibilities for early diagnosis, monitoring disease progression and developing personalized treatment strategies. Continued research and technological advancements are essential to overcome current challenges and fully realize the potential of biomarkers in improving the lives of patients with Alzheimer's disease.

Literature Review

In Alzheimer disease, α-synuclein is a key biomarker. Aggregated forms of α-synuclein in CSF and blood are linked to PD pathology. DJ-1, a protein associated with oxidative stress and neurofilament light chain, indicative of neuronal damage, are also potential biomarkers for diagnosis and disease progression. Parkinson's disease is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, bradykinesia, rigidity and postural instability, along with non-motor symptoms including cognitive impairment, mood disorders and autonomic dysfunction. The complexity and variability of PD make it challenging to diagnose and manage. Molecular biomarkers have emerged as crucial tools in understanding the pathogenesis of PD, improving diagnosis, monitoring disease progression and developing targeted therapies.

Alpha-Synuclein (α-synuclein) is a protein primarily found in the brain, where it plays a role in synaptic function. The aggregation of misfolded α-synuclein into Lewy bodies is a pathological hallmark of PD. DJ-1 is a protein involved in protecting cells from oxidative stress [3,4]. Mutations in the DJ-1 gene are linked to familial forms of PD. Neurofilament light chain is a structural protein released into the CSF and blood following neuronal damage. Elevated NfL levels are indicative of neurodegeneration and are associated with disease progression in PD. Mutations in the GBA gene, which encodes the lysosomal enzyme glucocerebrosidase, are a significant genetic risk factor for PD. Neuroinflammation is a key feature of PD pathology. Various inflammatory markers, such as cytokines and chemokine, are being studied as potential biomarkers.

Discussion

Multiple sclerosis biomarkers include oligoclonal bands in CSF, which are indicative of an immune response within the central nervous system. Serum levels of neurofilament light chain are being studied as a marker for neuronal injury and disease activity. These biomarkers help in diagnosing MS, predicting relapses and monitoring treatment efficacy. In stroke, early diagnosis and intervention are crucial. Biomarkers such as S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein are associated with brain injury and can help in the rapid diagnosis of ischemic stroke. Additionally, matrix metalloproteinase and inflammatory cytokines like Inter Leukin-6 (IL-6) are studied for their role in stroke prognosis and recovery. Molecular biomarkers are paving the way for personalized medicine in neurology [5]. By identifying specific biomarkers associated with an individual's disease, treatments can be tailored to achieve the best outcomes. For example, in AD, patients with high levels of amyloid plaques may benefit from anti-amyloid therapies, while those with tau pathology may respond better to tau-targeted treatments.

Biomarkers play a crucial role in drug development by serving as surrogate endpoints in clinical trials. They help in identifying target populations, monitoring drug efficacy and ensuring safety. In PD, for instance, biomarkers like α-synuclein and NfL can be used to assess the impact of neuroprotective therapies. Longitudinal studies using biomarkers can provide insights into the natural history of neurological diseases [6]. This understanding helps in developing strategies to slow or halt disease progression. In MS, monitoring NfL levels over time can help in adjusting therapies to minimize neuronal damage and improve patient outcomes. Despite the promise, there are challenges in the clinical application of molecular biomarkers. Variability in biomarker levels due to genetic, environmental and methodological factors can affect their reliability. Standardization of assay techniques and validation in large, diverse populations are essential steps forward.

Conclusion

Molecular biomarkers are transforming the field of neurology by providing deeper insights into the mechanisms of brain disorders and enabling more precise and personalized treatment approaches. Continued research and technological advancements hold the potential to overcome current challenges, ultimately improving the lives of patients with neurological diseases. The future of molecular biomarkers in neurology looks promising with advances in technologies like next-generation sequencing, proteomics and metabolomics. Integrating multi-omics data with clinical and imaging findings through artificial intelligence and machine learning will further enhance the precision of diagnosis and treatment.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Van Schependom, Jeroen and Miguel D’haeseleer. "Advances in neurodegenerative diseases." J Clin Med 12 (2023): 1709.

Google Scholar, Crossref, Indexed at

2. Zetterberg, Henrik and Barbara B. Bendlin. "Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies." Mol Psychiatry 26 (2021): 296-308.

Google Scholar, Crossref, Indexed at

3. Kordower, Jeffrey H., C. Warren Olanow, Hemraj B. Dodiya and Yaping Chu, et al. "Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease." Brain 136 (2013): 2419-2431.

Google Scholar, Crossref, Indexed at

4. Engelborghs, Sebastiaan, Ellis Niemantsverdriet, Hanne Struyfs and Kaj Blennow, et al. "Consensus guidelines for lumbar puncture in patients with neurological diseases." Alzheimer’s Dement 8 (2017): 111-126.

Google Scholar, Crossref, Indexed at

5. Mollenhauer, Brit, Richard Batrla, Omar El‐Agnaf and Douglas R. Galasko, et al. "A user's guide for α‐synuclein biomarker studies in biological fluids: Perianalytical considerations." Mov Disord 32 (2017): 1117-1130.

Google Scholar, Crossref, Indexed at

6. Thijssen, Elisabeth H., Renaud La Joie, Amy Wolf and Amelia Strom, et al. "Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration." Nat Med 26 (2020): 387-397.

Google Scholar, Crossref, Indexed at