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.
To investigate whether inhibiting BACE1 in adults might be less harmful, Yan and colleagues generated mice that gradually lose this enzyme as they grow older.
These mice developed normally and appeared to remain perfectly healthy over time.
Researchers at the Cleveland Clinic Lerner Research Institute have found that gradually depleting a specific enzyme in the brain could be the key to undoing the damage caused by the debilitating brain disease.
BACE1, also known as beta-secretase, helps produce these plaques by splitting amyloid precursor protein (APP) into beta-amyloid peptide - a process called cleaving.
Work on the prodromal trial continued following the earlier flop in the hope patients who were yet to develop full-blown Alzheimer's might respond better to the drug. Once it was established that these animals developed healthily they were bred with other mice that had been bred to develop amyloid plaques when they hit 75 days old.
Loss of BACE1 also improved the learning and memory of mice with Alzheimer's.
A new study has successfully reversed both the biological and behavioral hallmarks of Alzheimer's disease in mouse models. Closer inspection of neuronal activity did reveal that reducing BACE1 activity did not completely restore synaptic functions and the researchers do suggest that caution is still warranted as the enzyme does seem to be fundamental for optimal cognitive function. In addition, there was significant improvement in synaptic functions, as determined by long-term potentiation and contextual fear conditioning experiments, in association with the reversal of amyloid plaques.
The results were remarkably positive, with the reduction in BACE1 activity not only stalling the development of amyloid plaques in the mice, but actually removing the deposits that had already formed.
"Hence, this knowledge provides a strong foundation for the concept that BACE1 inhibitors should be administered to humans as early as possible to prevent or reverse amyloid deposition". "If your brain has deteriorated such that your ability to remove those plaques is gone, then BACE1 may have very limited usefulness".
There's reason to be hopeful because BACE1 performs much the same function in mice and men, said Dr. Ezriel Kornel, director of The Orthopedic and Spine Institute at Northwell Health's Northern Westchester Hospital in Mount Kisco, N.Y.