P 236 - Oxidative Stress Markers of Alzheimer's Disease in Peripheral Cell Mitochondria

Abstract

Alzheimer's disease (AD) represents a neurodegenerative disease leading to progressive dementia in the elderly. AD has been associated with increased oxidative stress and mitochondrial dysfunction. Hence, markers for oxidative stress are expected to accumulate not only in brain mitochondria, but also in mitochondria of peripheral cells. We have developed and optimized a method for the rapid and selective fluorogenic derivatization and enrichment of specific protein oxidation products, 3-nitrotyrosine and 3,4-dihydroxyphenylalanine (DOPA), in order to quantitatively compare protein oxidation in the mitochondria of peripheral, white blood cells obtained from healthy donors, patients with mild cognitive impairment (MCI), and AD patients. Double blind studies reveal a ca. two-fold increase of protein nitration/oxidation between mitochondrial proteins derived from healthy volunteers and MCI patients, with no further increase between MCI and AD patients. Proteomic studies will show whether specific proteins are target for nitration/oxidation during the pathogenesis of MCI and AD. Mitochondrial protein nitration/oxidation may be used for early screening of patients with the genetic risk for the development of AD or as companion diagnostic for pharmacological interventions.