ABSTRACT
This chapter introduces the reader to neurodegenerative diseases linked to dementia or movement disorders in which a protein or proteins containing mutations have been identified as causative factors of the disease. The specific mechanisms for those vulnerabilities are still unknown, but together they illustrate a variety of molecular pathways, triggered perhaps by aggregation of specific proteins, that lead to neurodegenerative syndromes. Mutation or overexpression of a-synuclein leads to cytoplasmic inclusions of presumably misfolded a-synuclein recognized histologically as Lewy bodies (LB). Tau is present in the brain in six major isoforms derived from alternative splicing of a single tau gene. The mutations in the tau gene that cause missense amino acid substitutions tend to cluster around the microtubule-binding domains of tau. Alzheimer's Disease (AD) is the most common neurodegenerative disease, with over 4 million Americans affected.
