Mitochondrial Dysfunction and Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that culminates in selective neuronal loss in discrete regions of the brain. AD is genetically heterogeneous and is best characterized as a syndrome with a common but variable pathologic sequela. Rare familial forms of AD follow conventional patterns of autosomal dominant Mendelian inheritance (St. George-Hyslop et al., 1990; Schellenberg et al., 1992; Levy-Lahad et al., 1995a,b), occur earlier in life and account for less than 5% of all AD cases. The vast majority of AD cases (approximately 95%) appear late in life after the age of 60, without clearly discernible chromosomal linkages. However, first-degree relatives of affected probands are at higher risk for AD than the general population (Silverman et al., 1994a,b) and lack of a family history is a negative risk factor for AD (Payami et al., 1994). Further, the risk of AD increases when a maternal relative is afflicted with AD (Duara et al., 1993; Edland et al., 1996). Sporadic inheritance with familial association, maternal transmission, and variable phenotypic expression are hallmarks of mitochondrial genetic disease (Johns, 1995; Luft, 1994). These features typify the mode of genetic presentation of late-onset AD in the population.