Classification of CNS degenerative diseases is moving from a system where diseases are grouped by symptoms to a system where diseases are classified by the underlying pathologic protein. Most degenerative diseases are caused by abnormalities of the proteins/peptides beta-amyloid, tau or alpha-synuclein. The underlying pathology of degenerative diseases causing cognitive impairment is reviewed with an eye toward better understanding the underlying biological process. Symptoms suggestive of specific protein abnormalities are reviewed. Emphasis is placed on how linking these symptoms with the pathologic protein will be relevant to evolving treatment strategies for these diseases.