Mitochondrial involvement in Alzheimer's disease

The causes of most neurodegenerative diseases, including sporadic Alzheimer 's disease (AD), remain enigmatic. There is, however, increasing evidence i mplicating mitochondrial dysfunction resulting from deafferentiation of dis connected neural circuits in the pathogenesis of energy deficit in AD. The patterns of reduced expression of both mitochondrial DNA (mtDNA) and nuclea r DNA (nDNA) encoded genes is consistent with a physiological down-regulati on of the mitochondrial respiratory chain in response to reduced neuronal a ctivity. On the other hand, the role(s) of somatic cell or maternally inher ited mtDNA mutations in the pathogenesis of mitochondrial dysfunction in AD are still controversial. (C) 1999 Elsevier Science B.V. All rights reserve d.