Scientists report that they have managed to slow disease progression and reduce formation of amyloid plaques in worm and mouse models of Alzheimer’s disease by boosting mitochondria defense against a particular form of protein stress. Their findings were published yesterday in Nature.
These results build on a recent research trend of exploring metabolic solutions to treat Alzheimer’s disease. During normal aging and age-associated diseases, cells face damage and struggle to replace mitochondria. Since mitochondria provide energy to brain cells, this damage could leave the brain vulnerable to Alzheimer’s.
The scientists, working in Johan Auwerx's lab at EPFL, tested the effects of the antibiotic doxycycline and the vitamin nicotinamide riboside, which are known to turn on defense pathways that protect against excessive mitochondrial damage in Alzheimer’s disease models.
In treated worms, health, performance and lifespan was increased compared to a control group and plaque formation was significantly reduced. Similar results were observed in cultured human cells using the same treatment combination.
Next, the researchers performed a similar experiment in mice. Not only was mitochondrial function improved and plaque formation increased, but the mouse experiments also demonstrated a marked normalization in cognitive function.
"We have shown that restoring mitochondrial health reduces plaque formation—but, above all, it also improves brain function, which is the ultimate objective of all Alzheimer's researchers and patients," said Johan Auwerx.
These results may offer novel targets for treating Alzheimer's disease in humans.
Image: Whole-brain hemisphere sections of Alzheimer's mice, the model APP/PSEN1, before and after treatment with the NAD+ booster Nicotinamide riboside (NR). The beta-amyloid plaque content in the brain of the APP/PSEN1 mice (left), clearly visible by Thioflavin S staining in green color and associated to brain damage during the disease, is reduced after 10 weeks treatment with NR (right). Image courtesy of: Vincenzo Sorrentino, Mario Romani, Francesca Potenza/EPFL.