Chapter 21 - Concepts and classification of neurodegenerative diseases

Abstract

Neurodegenerative diseases are disorders characterized by progressive loss of neurons associated with deposition of proteins showing altered physicochemical properties in the brain and in peripheral organs. Molecular classification of neurodegenerative disease is protein-based. This emphasizes the role of protein-processing systems in the pathogenesis. The most frequent proteins involved in the pathogenesis of neurodegenerative diseases are amyloid-β, prion protein, tau, α-synuclein, TAR-DNA-binding protein 43kDa, and fused-in sarcoma protein. There are further proteins associated mostly with hereditary disorders such as proteins encoded by genes linked to trinucleotide repeat disorders, neuroserpin, ferritin, and familial cerebral amyloidoses. The clinical presentations are defined by the distinct involvement of functional systems and do not necessarily indicate the molecular pathologic background. Seeding of pathologic proteins and hierarchic involvement of anatomic regions is commonly seen in neurodegenerative diseases. Overlap of neurodegenerative diseases and combinations of different disorders is frequent. Translation of neuropathologic categories of neurodegenerative diseases into in vivo detectable biomarkers is only partly achieved but intensive research is performed to reach this goal.