Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS), and Frontotemporal Dementia (FTD) present significant clinical challenges due to their complex genetic underpinnings. This study investigates the genetic mutations associated with these diseases and evaluates therapeutic responses across a cohort of 400 patients. We identified distinct mutation profiles for each disease, with APP and PSEN1 mutations prevalent in Alzheimer’s, LRRK2 and SNCA in Parkinson’s, and C9orf72, TDP-43, and FUS in ALS and FTD. Statistical analysis revealed a correlation between specific genetic mutations and disease severity, with therapeutic efficacy varying across treatment types. Disease-modifying drugs showed moderate effectiveness, while symptomatic treatments provided the highest response rates. This research highlights the genetic diversity underlying neurodegenerative diseases and underscores the need for tailored therapeutic approaches. By linking genetic mutations to clinical outcomes, our findings contribute to more targeted and effective treatment strategies, offering potential pathways for future research and therapeutic development.