Misfolding and clumping of proteins in the brain has been linked to various neurodegenerative diseases, these include Alzheimer' s disease (AD), Parkinson' s disease (PD) and amyotrophic lateral sclerosis (ALS). In pathological, these neurodegenerative diseases are related to protein misfolding and aggregation. AD is pathologically characterized by abnormal aggregation of ß -amyloid protein and tau protein neurofibrillary tangles in the brain, and PD is pathologically related to abnormal aggregation of a-synuclein in dopaminergic neurons in the brain. The misfolding of specific protein, such as transactive response element DNA binding protein-43 (TDP-43) and inclusion body formation, is one of the markers of ALS. Sleep disorder is not only a concomitant symptom of patients with these diseases, but also a precursor symptom of the onset of these diseases. This review elaborates on the abnormal protein aggregation characteristics and sleep disorder features of AD, PD, and ALS, and summarizes the potential of sleep disorder in early diagnosis and treatment of these diseases. Sleep disorder may become early diagnostic clues and treatment entry point for neurodegenerative diseases.