Lower mitochondria gene activity in brains with Alzheimer's disease

Brain tissue from Alzheimer's disease patients shows reduced expression of nuclear genes coding for mitochondrial function, according to researchers.

They say that their findings show some of the earliest cellular changes in the development of Alzheimer's disease, and could be used to aid diagnosis as well as increasing understanding of the disease.

'Age-related neurodegenerative diseases, like Alzheimer's, progress over a long period of time before they become clinically apparent,' said Dr Diego Mastroeni of Arizona State University, one of the authors of the study. 'Findings from our laboratory have uncovered early expression changes in nuclear-encoded, but not mitochondrial-encoded, mRNAs occurring in one's early 30s, giving us a glimpse into what we suspect are some of the earliest cellular changes in the progression of Alzheimer's disease.'

Researchers examined gene expression in tissue samples from the hippocampus, the brain structure responsible for memory, which is severely affected by Alzheimer's disease. They compared samples from 44 normal brains of people aged 29–99 years, ten with mild cognitive impairment (an intermediate stage between normal ageing and dementia) and 18 with Alzheimer's disease.

They found different levels of expression in genes in the nucleus that are needed to generate energy from mitochondria. Hippocampal tissue from Alzheimer's disease and normally ageing brains showed substantially lower expression of these genes.

However, tissue from brains with mild cognitive impairment, which can be a precursor to Alzheimer's disease, showed higher expression of the genes. The researchers suggest this may be a compensation against the early development of the disease.

Earlier studies had shown the accumulation of amyloid beta protein in neurons, a hallmark feature of Alzheimer's disease, directly interfere with mitochondrial function.

'Our work on mitochondria offers the promise of a reliable marker appearing earlier in the course of the disease – one which more closely correlates with the degree of dementia than the current diagnostic of plaques and tangles,' said Professor Paul Coleman of Arizona State University, one of the authors of the study.

The researchers suggest that restoring the function of these genes could potentially slow development of Alzheimer's disease, but that much more research is needed.

The study was published in Alzheimer's and Dementia.