Background: Neurodegenerative disorders present a substantial worldwide health obstacle. Neurodegenerative disorders, namely Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are typified by a gradual nervous system deterioration, resulting in a decline in cognitive function, impaired motor abilities, and eventual incapacitation. Clinical signs and neuroimaging may not be sensitive or specific enough to diagnose certain diseases early. Thus, reliable biomarkers are needed to identify responsive individuals and provide a prognosis. This investigation aimed to create innovative diagnostic indicators for promptly identifying and predicting neurodegenerative ailments. Materials and Methods: This multi-disciplinary study identified and validated neurodegenerative disease diagnostic indicators (i.e. Alpha-synuclein, Apolipoprotein E and Cytokines). A systematic literature analysis identified disease pathology and progression-associated biomarkers. These indicators were tested using ELISA method and all the tests were performed as per the kit standard protocol. Samples were collected from neurodegenerative disease patients and healthy controls. Statistical analyses determined the indicators' diagnostic and prognostic accuracy. Results: Preliminary findings from our study revealed several promising diagnostic markers for neurodegenerative diseases. These markers showed significant alterations in their expression or levels in patients compared to healthy controls. Additionally, we observed correlations between marker levels and disease severity, suggesting their potential prognostic value. Furthermore, combining multiple markers showed improved diagnostic accuracy compared to individual markers alone. Conclusion: New neurodegenerative disease diagnostic indicators might enhance patient outcomes. This study's indicators may reveal disease pathways and be therapeutic targets. To prove these indicators' clinical value, bigger and more varied cohorts would be helpful. Neurodegenerative disease diagnosis and prognosis would be advantageous. This might assist at-risk persons in obtaining prompt interventions and targeted therapy.