Synapse is a basic structural and functional component for neural communication in the brain. To initiate and maintain continuous functional neural information flow, the presynaptic terminal is a structurally and functionally essential place as an initiator for communication. It contains synaptic vesicles (SV) filled with neurotransmitter, active zone for release place, and a number of proteins for SV fusion and retrieval. The structural and functional synaptic plasticity is one of the representative characteristics however it is also highly vulnerable in various pathological circumstances. In fact, synaptic alteration is thought to be central to the neural disease process. In particular alteration of the structural and functional phenotype of the presynaptic terminal is one of the most significant evidence for neural diseases. In this review, we specifically describe structural and functional alteration of nerve terminals in several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD).