Mitochondrial Involvement in Neurodegenerative Dementia

Neurodegenerative disorders include progressive, age-dependent brain disorders, clinically characterized by cognitive decline, variable patterns of motor impairment and irreversible changes in behavior and personality. Pathological hallmarks of these disorders including dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are accumulations in specific brain areas of mutant proteins such as α-synuclein, extracellular β-amyloid, and intracellular hyperphosporylated tau, mutant huntingtin, TAR DNA binding protein and superoxide dismutase respectively. This chapter reports the evidence for mitochondrial involvement in the most common form of neurodegenerative dementia, represented by AD and DLB. Precocious mitochondrial dysfunction and consequent bioenergetic dysfunction and ROS overproduction has been demonstrated in the triple transgenic mouse model of AD in an early disease phase. LRRK2 is suggested to play a crucial role in the pathology of both familial and sporadic α-synucleinopathies, including DLB