Neurodegenerative diseases are a group of age-related disorders characterized by the progressive degeneration or death of neurons in the central or peripheral nervous system. The prevalence of these diseases is increasing due to an aging population, leading to growing economic burdens on healthcare systems. Current treatments are mostly symptomatic and do not address the underlying causes, with limited effect on disease progression. Recent advances in neurobiology and neurogenetics have provided valuable insights into the pathogenesis of these diseases, which are influenced by genetic, environmental, and lifestyle factors. This Special Issue focuses on Alzheimer's disease (AD), the most common cause of dementia, characterized by memory loss, behavioral disturbances, and impaired judgment. The presence of senile plaques and neurofibrillary tangles are key neuropathological hallmarks of AD. Early and accessible diagnostic methods, such as the QPLEX™ kit, are crucial for preventive interventions. The kit detects amyloid-β1-40, galectin-3 binding protein, angiotensin-converting enzyme, and periostin in peripheral blood, aiding in early diagnosis. Other studies in the Special Issue explore new therapeutic approaches for AD and other neurodegenerative diseases. For example, Nicole E. Eassa and colleagues developed a viral-mediated approach to express mutated human genes contributing to AD pathology in rats, showing potential for treating comorbid psychosis in AD patients. Houa-Yan Wang and colleagues investigated simufilam, a novel oral drug candidate that disrupts abnormal FLNA receptor interactions, reducing Aβ42 binding to α7nAChR and inflammatory cytokine release. The issue also covers Parkinson's disease (PD), focusing on reducing alpha-synuclein levels and enhancing autophagy. Ibrar Siddique and colleagues identified ARL6IP5 as a novel regulator of neuronal autophagy, which reduces α-synuclein aggregation and improves cell survival in PD models. Prachayaporn Prasertsuksri and colleagues found that andrographolide has significant neuroprotective effects against neurotoxin MPP+, potentially as a supplement for PD prevention. Additionally, the issue includes studies on amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), highlighting the involvement of specific proteins and signaling pathways in their pathophysiology. The Special Issue concludes with discussions on the general mechanisms of neurodegeneration, including the role of protein aggregation and the potential for therapeutic interventions targeting these mechanisms. Overall, the research aims to advance the understanding of neurodegenerative diseases and develop more effective treatments.Neurodegenerative diseases are a group of age-related disorders characterized by the progressive degeneration or death of neurons in the central or peripheral nervous system. The prevalence of these diseases is increasing due to an aging population, leading to growing economic burdens on healthcare systems. Current treatments are mostly symptomatic and do not address the underlying causes, with limited effect on disease progression. Recent advances in neurobiology and neurogenetics have provided valuable insights into the pathogenesis of these diseases, which are influenced by genetic, environmental, and lifestyle factors. This Special Issue focuses on Alzheimer's disease (AD), the most common cause of dementia, characterized by memory loss, behavioral disturbances, and impaired judgment. The presence of senile plaques and neurofibrillary tangles are key neuropathological hallmarks of AD. Early and accessible diagnostic methods, such as the QPLEX™ kit, are crucial for preventive interventions. The kit detects amyloid-β1-40, galectin-3 binding protein, angiotensin-converting enzyme, and periostin in peripheral blood, aiding in early diagnosis. Other studies in the Special Issue explore new therapeutic approaches for AD and other neurodegenerative diseases. For example, Nicole E. Eassa and colleagues developed a viral-mediated approach to express mutated human genes contributing to AD pathology in rats, showing potential for treating comorbid psychosis in AD patients. Houa-Yan Wang and colleagues investigated simufilam, a novel oral drug candidate that disrupts abnormal FLNA receptor interactions, reducing Aβ42 binding to α7nAChR and inflammatory cytokine release. The issue also covers Parkinson's disease (PD), focusing on reducing alpha-synuclein levels and enhancing autophagy. Ibrar Siddique and colleagues identified ARL6IP5 as a novel regulator of neuronal autophagy, which reduces α-synuclein aggregation and improves cell survival in PD models. Prachayaporn Prasertsuksri and colleagues found that andrographolide has significant neuroprotective effects against neurotoxin MPP+, potentially as a supplement for PD prevention. Additionally, the issue includes studies on amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), highlighting the involvement of specific proteins and signaling pathways in their pathophysiology. The Special Issue concludes with discussions on the general mechanisms of neurodegeneration, including the role of protein aggregation and the potential for therapeutic interventions targeting these mechanisms. Overall, the research aims to advance the understanding of neurodegenerative diseases and develop more effective treatments.