Published: Thu, February 15, 2018
Medicine | By Brett Sutton

Staying physically fit may help keep Alzheimer's disease at bay

Staying physically fit may help keep Alzheimer's disease at bay

There was one ringing endorsement this morning for BACE1 as a prospect to tackle Alzheimer's: a team at Cleveland Clinic published a paper showing they had successfully reversed Alzheimer's in a middle-aged lab mouse.

'We were surprised it worked so well, we saw complete reversal, ' Yan, who will start as chair of the department of neuroscience at the University of CT this spring, said.

As BACE1 plays a role in beta-amyloid production, several companies are trying to develop drugs that block the enzyme.

In addition, other teams at the O'Donnell Brain Institute are designing tests for the early detection of patients who will develop dementia, and seeking methods to slow or stop the spread of toxic proteins associated with the disease such as beta-amyloid and tau, which are blamed for destroying certain groups of neurons in the brain.

BACE1 does this by "cleaving", or breaking down, a protein called amyloid precursor protein.

The scientist began by creating mice genetically programmed to lose BACE1 slowly as they age.

The results of this laboratory experiment have now been published in the Journal of Experimental Medicine.

These mice developed normally and appeared to remain perfectly healthy over time.


Lead author Riqiang Yan admitted he was "shocked" when their attempts to reduce amyloid plaque in mice completely eradicated the unsafe build-ups that slowly cripple the brain.

Scientists also used brain imaging to measure the functionality of each patients white matter.

This was not the only sign of Alzheimer's that the enzyme loss helped to reverse: the mice's levels of beta-amyloid peptide also dropped, and microglia - brain cells that, when activated, had previously correlated with amyloid plaque density - were now deactivated.

BACE1 plays a vital role in the formation of beta-amyloid brain plaques.

MSD confirmed that it will discontinue the Phase III APECS study, assessing the investigational BACE1 inhibitor in people with prodromal Alzheimer's disease (AD), on the recommendation of an external Data Monitoring Committee. But as they got older and lost more and more of the BACE1 enzyme, their plaques started to gradually disappear.

The findings could be a game changer for the pharmaceutical industry, which has had a rough ride with BACE1 inhibitors - although some analysts claim Merck's failure suggests we are barking up the wrong tree.

"Future studies", Yan says, "should develop strategies to minimize the synaptic impairments arising from significant inhibition of BACE1 to achieve maximal and optimal benefits for Alzheimer's patients".

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