The last year since our most recent Alzheimer’s research update has seen some important new developments in the fight against Alzheimer’s disease. Drug trial results, promising new studies, and an exciting new screening test are just some of the things happening in the Alzheimer’s research world. We help caregivers, home care aides and loved ones stay informed and stay hopeful about the fight against Alzheimer’s disease.
Since the beginning of 2018, two separate drug trials of once-promising Alzheimer’s drugs were deemed failures. Three trials of the drug idalopirdine, and one of the drug solanezumab, all failed to show results in long-term trials. Pfizer has even announced they will stop pursuing an Alzheimer’s drug altogether, citing scientific and financial frustration. The director of global science initiatives at the Alzheimer’s Association, James Hendrix, says that both these drugs attacked the formation of amyloid plaque in the brain, based on the wide-spread assumption that removing plaque would slow or halt the progression of the disease. Alzheimer’s research has been targeting the amyloid plaque for more than ten years, but the failure of these drugs to slow memory loss and thinking decline in trial subjects has scientists questioning this approach. One fundamental principle of research begun years ago was the assumption that patients showing cognitive decline had plaque in the brain, based on autopsy results. But recent studies with PET scans ultimately showed that 30% of these patients had no plaque at all, which makes the premise of targeting the plaque faulty. While the failure of these two drugs is highly disappointing, research on what causes plaque to develop in the first place and stopping it may get more support and better results.
Researchers at the Cleveland Clinic completed a study on mice that targeted and removed just one enzyme in the brain, called BACE1, which helps make beta-amyloid peptides in the brain. Based on studies that showed stopping or reducing the activity of that enzyme reduces the production of beta-amyloid peptides, researchers tested the process in mouse brains. The study deleted the gene that produces BACE1 completely, and then used BACE1 inhibitors to slowly lower the levels of the enzyme in the brain. This led to reduced neuron loss and better brain function in the mice, after almost completely removing the deposits of plaque in the brain. Scientists are hopeful, but past experience shows that success with mice doesn’t always translate to humans. There are currently five trials in progress with humans and various compounds of BACE1 inhibitors.
As we mentioned above, there are few ways to test plaque development and presence on living patients, making research and trials more expensive and more difficult. Positron emission tomography imaging (PET scan) is expensive, and sampling cerebrospinal fluid (CSF) with a lumbar puncture or spinal tap is painful and bears a tiny risk to the patient. A study conducted by Japanese and Australian scientists reported last month that a blood screening test can predict the levels of amyloid beta long before symptoms begin to show and can reveal whether the patient is developing Alzheimer’s or another form of dementia. The senior author of the study believes that “enough amyloid penetrates the blood–brain barrier to make its way into the bloodstream to be a useful measure of cognitive function.” The blood test is far less expensive than the current tests, and can also indicate pre-clinical, or pre-symptom, levels of amyloid beta more easily. The study proved that the level of amyloid present in blood matched both the level of cognitive decline and the level found by PET scan and CSF sample. A non-invasive amyloid test means more access to trials, more representative trial demographics, and more variation in trial patients, all of which will contribute to better and more successful research.