Alois Alzheimer, a German physician in 1906, was studying a woman who came to his clinic complaining about memory loss, language problems, and behavioral changes. She ultimately died of complications from her illness. After her death, Dr. Alzheimer examined her brain and found abnormal protein clumps, now referred to as amyloid deposits, and bundles of fibers, now called neurofibrillary tangles. The dementia exhibited by this patient acquired the name Alzheimer’s dementia because of its discovery by Dr. Alzheimer.
In current studies of post mortem brains from patients who have died from Alzheimer’s disease, the research also revealed amyloid deposits and neurofibrillary tangles in almost all cases. These two protein accumulations are considered the major hallmarks of Alzheimer’s disease.
At the beginning of the disease process, these protein accumulations appear mainly in the hippocampus, a brain region that is critical in learning and the formation of memories. As the disease spreads, so do these protein deposits to other brain regions. Other studies have revealed multiple cellular changes – including synapses that lose their ability to connect with synapses from other brain cells — in the brains of patients with early-onset familial Alzheimer’s and late-onset sporadic Alzheimer’s. Synaptic loss has been found to be the best correlate of cognitive decline in patients with Alzheimer’s.
During the last three decades, Alzheimer’s researchers have worked to better understand how both amyloid beta and another protein called tau are associated with cognitive decline in Alzheimer’s disease.
Some researchers believe amyloid beta plays the more important role; other researchers believe tau also plays a very important role.
Recent clinical trials that focused on using drug inhibitors to limit amyloid beta levels in the brain were disappointing; the drugs did not improve patients’ cognitive function.
But those trials raised important questions in Alzheimer’s research:
- Are the drugs targeting the right kind of amyloid beta?
- Might the drugs help if patients were given them earlier, before the disease had advanced so far?
- What might be the long-term consequences of these drugs, and
- Do we need to better understand how tau might be affecting brain synapses, before we see clinical symptoms of Alzheimer’s?
I also believe that to better understand synaptic loss in Alzheimer’s, the interaction of amyloid beta and tau with each other needs to be better researched. My colleague and I recently published an article in the Journal of Alzheimer’s Disease that explored that question. My laboratory looked for evidence of amyloid beta and tau interactions. And we found that the Alzheimer’s disease process was strongest where those interactions happened.
More research needs to focus on molecules that might prevent or affect that amyloid beta/tau interaction. Those molecules might end up being an important treatment for Alzheimer’s, as they could significantly improve cognitive and memory functions for people who have this debilitating disease.