Alzheimer's disease (AD) represents one of the major health problems of the older population. Progressive memory decline is one of the hallmark clinical features of the disorder, and results in suffering for patients as well as caregivers. No effective treatment is available, and the etiology remains unknown. Preliminary work at our institution has resulted in the identification of a deficient mitochondrial enzyme, cytochrome oxidase (CytOx), in platelets and brain tissue of small samples of patients with AD. CytOx is a complex enzyme within the mitochondrial electron transport chain that is essential to normal neuronal function, and it is hypothesized that this deficiency may represent a biochemical lesion that is specific to AD. Whether this deficiency if fundamentally related to level of dementia and degree of memory disturbance is unknown. The proposed project will include 100 patients with a diagnosis of probable AD, 50 healthy controls, and 50 patients with Parkinson's disease. First, the sensitivity and specificity of CytOx deficiency in AD will be evaluated. Second, we will examine the degree of dementia and level of memory impairment in relation to CytOx levels in the AD and control groups. Additional analyses will focus on the longitudinal changes in CytOx and memory functioning in each of the groups over a two year period in order to examine whether decreases in CytOx values are associated with concomitant changes in cognitive and memory function. Strong relationships between level of cognitive and memory dysfunction and CytOx deficiency are expected. These studies may result in a useful diagnostic test for AD, in addition to enhancing our understanding of memory decline in the disease, and may have further implications for potential treatment avenues in the future.
