Electrophysiological biomarkers in neurodegenerative diseases: recent advances and clinical implications

Electrophysiological biomarkers are critical tools for understanding and diagnosing major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and Huntington's disease. These biomarkers reveal early disruptions in neural circuits before overt clinical symptoms become apparent. In Alzheimer's disease, electrophysiological changes such as hippocampal hyperexcitability, impaired synaptic plasticity, and disrupted theta-gamma oscillations strongly correlate with cognitive deficits and underlying pathological features like amyloid-beta and tau aggregation. Parkinson's disease is characterized by abnormal burst firing patterns of dopaminergic neurons, exaggerated beta oscillations within basal ganglia circuits, and impaired cortico-striatal synaptic plasticity, reflecting the effects of dopamine depletion and alpha-synuclein pathology. ALS demonstrates distinct electrophysiological features, notably hyperexcitability of motor neurons and impaired neuromuscular transmission, linked to mutant superoxide dismutase 1 and transactive response DNAbinding protein-43. Huntington's disease shows pronounced dysfunction in striatal circuits, marked by excitationinhibition imbalance and altered glutamatergic signaling, driven by mutant huntingtin toxicity. Collectively, these electrophysiological biomarkers provide early diagnostic insights and deepen our understanding of disease mechanisms, paving the way for targeted therapeutic interventions and improving the management and prognosis of neurodegenerative diseases.