New research has revealed that certain nuclear genes responsible for mitochondrial respiration processes are downregulated in Alzheimer's patients
Mitochondrial function is essential, and when things go wrong it has a severe impact on cellular, and organismal health. Mitochondrial dysfunction is a known hallmark of aging and is therefore associated with a range of age-related diseases. Now research has revealed mitochondrial function, or a downtuning of it, could be a driving factor in Alzheimer's progression.
"Age-related neurodegenerative diseases, like Alzheimer's, progress over a long period of time before they become clinically apparent. The earliest physiological and molecular events are largely unknown. Findings from our laboratory have uncovered early expression changes in nuclear encoded, but not mitochondrial encoded mRNAs occurring in one's early thirties; giving us a glimpse into what we suspect are some of the earliest cellular changes in the progression of Alzheimer's disease"
In a new study published in the journal Alzheimer's and Dementia, researchers have outlined that specific types of genes associated with mitochondrial cell respiration (essentially the energy making process) are reduced in expression in people with Alzheimer's compared to healthy individuals. Interestingly, this reduction of expression was confined to nuclear mitochondrial genes, rather than mitochondrial genes themselves (found in the tiny mitochondrial genome). The team also discovered that in patients with mild cognitive impairment, in the intermediate stages, these genes were revved up - suggesting there is some kind of compensatory mechanism initially.
How was the study performed?
In order to study these precise differences in gene expression, the scientists examined tissue sourced from the hippocampus. 44 patients were used in the study aged 29-99 years and consisting of 18 individuals with Alzheimer's disease and 10 with mild cognitive impairment.
Which genes are involved?
The team compared both mitochondrial genome genes and nuclear genes that encode for mitochondrial proteins. They found that those genes involved with a process called oxidative phosphorylation (the main route of energy production) were being expressed substantially lower in Alzheimer's patients. We already know that oxidative phosphorylation appears to drop in older brains, but this process has not been tied to Alzheimer's before. A reason for the drop may possibly be the accumulation of toxic amyloid beta molecules, which are implicated in mitochondrial dysfunction. These may somehow interfere with correct transport of nuclear encoded proteins to mitochondria - which could have a knock on effect on nuclear expression.
"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"
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