Last updated February 15, 2018 at 11:11 am
Current drugs used to treat Alzheimer’s disease, BACE1 inhibitors, could be far more effective thanks to new findings from mice experiments.
The brain of a 10-month-old mouse with Alzheimer’s disease (left) is full of amyloid plaques (red) surrounded by activated microglial cells (green). But these hallmarks of Alzheimer’s disease are reversed in animals that have gradually lost the BACE1 enzyme (right). Credit: Hu et al., 2018
BACE1 enzyme target
The drugs target an enzyme called BACE1, which forms a build-up of beta-amyloid peptide in the brain – one of the earliest events in Alzheimer’s disease. By gradually depleting BACE1 in the brains of mice with Alzheimer’s disease, researchers completely reversed the formation of amyloid plaques. This improved the mice’s cognitive function, learning, and memory. Plus it reversed other markers of Alzheimer’s disease like activating microglial cells and forming abnormal neuronal processes.
Researcher Riqiang Yan notes the importance of this finding; “To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer’s disease mouse models.”
Alzheimer’s in mice
This discovery was not made by treating the mice with drugs, but by breeding them to express BACE1 in the desired way. First, the researchers bred mice that naturally lose BACE1 as they age, and proved that those animals were healthy and developed normally. Then they bred them with mice that would normally develop Alzheimer’s disease – but with less BACE1 the amyloid plaques disappeared. However, mice that completely lack BACE1 suffer sever neuro-developmental defects.
“Our data show that BACE1 inhibitors have the potential to treat Alzheimer’s disease patients without unwanted toxicity,” says Yan, “Future studies should develop strategies to minimize the synaptic impairments arising from significant inhibition of BACE1 to achieve maximal and optimal benefits for Alzheimer’s patients.”
Better treatment strategies
This information will be incredibly valuable in determining the optimal schedule for treatment with BACE1 inhibitors. The researchers suggest that to prevent or reverse amyloid deposits, the drugs should be administered as early as possible. But they call for caution because of the potential for adverse effects on cognitive function, pointing out that sequential and gradual increases in BACE1 inhibitors will likely show the greatest benefits.
Alzheimer’s disease is the most common form of dementia. Of the 420 000 Australians with dementia, up to 70 percent suffer from Alzheimer’s disease.
This research was published in the Journal of Experimental Medicine.
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