Upcoming studies for the treatment of Alzheimer's disease

Ronald C. Petersen, MD, PhD: Given the fact that we may not have fully explored all the avenues of the amyloid cascade hypothesis, we recently discussed some new trials that will be launched in order to intervene earlier in the process of the amyloid cascade.

For example, a study funded by the National Institute on Aging, using the consortium of Alzheimer's clinical trials, will launch a study called A45. This means that 2 drugs will be evaluated. Clinically normal people with amyloid in the brain will be eligible for this study. Again, normal people who have amyloid, for whom we want to prevent their clinical progression.

They will first receive a drug that will reduce amyloid in the brain – an antibody that will reduce amyloid in the brain. Once the amyloid levels have been knocked out, a second drug will be introduced to prevent them from forming new amyloids. So, an antibody and a BACE [beta secretase] the inhibitor will be used in sequence to see if you can slaughter the protein and keep it low; and I hope this will prevent the development of clinical symptoms. So it's a new way of thinking, a new clinical design, getting close to what's called preclinical space, which means that people have amyloid protein in the brain, but they're clinically normal.

Then there is another study under discussion that will probably be launched soon and that concerns people who are just below the positivity threshold for amyloid with PET. [positron emission tomography] scanning.

So far, we have talked about people with positive amyloid PET. But what about people who are just below the threshold, who are about to develop more amyloid, which can then trigger the accumulation of tau in the brain? So we think: can we measure this process? Can we see when amyloid is just starting to increase and can we see the tau going away with amyloid imaging? This may open the way for anti-tau or anti-amyloid therapy at this stage.

These are exciting trials that still focus on the cascade of amyloid / tau treatment. I think it's certainly a viable option to try to prevent the clinical symptoms of the disease.