Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology

Recent reports have suggested that mitochondrial dysfunction may contribute to the progression of the pathology of Alzheimer's disease (AD). However, both increases and decreases in the activity of cytochrome oxidase have bee n described in the hippocampi of AD patients. In this study we used immunoh istochemistry and quantitative autoradiographic methods to study the expres sion pattern of two cytochrome oxidase subunit proteins (nuclear-encoded CO X IV and mitochondrial-encoded COX I) in the hippocampus in relation to the development of AD-type pathology. We found heterogeneous expression of bot h COX subunits in AD with an increased expression of both subunit proteins in healthy, non-tangle-bearing, neurones but absence of both subunit protei ns in tangle-bearing neurones. Levels of COX IV but not of COX I were relat ed to the amount of hyperphosphorylated tau accumulated in the same hippoca mpal region but not to the amount of amyloid deposited in sporadic AD. In D own's syndrome COX I and COX TV were similarly increased in the presence of AD pathology in non-tangle-bearing neurones. However, in these cases level s of enzyme expression were correlated to the amount of amyloid accumulatio n but not the amount of hyperphosphorylated tau in the hippocampus. We beli eve that heterogeneity of expression of mitochondrial enzyme proteins betwe en neurones may contribute to the conflicting conclusions in previous repor ts regarding relative levels of cytochrome oxidase activity in the hippocam pus in AD. We hypothesise that the increased mitochondrial enzyme expressio n in healthy-appearing neurones of AD brains may represent a physiological. response to increased functional demand on surviving neurones as a consequ ence of AD-related neuronal pathology.