The prevailing focus in Alzheimer's disease (AD) research is on removal of amyloid, solid aggregates of misfolded proteins, considered the main agent of harm. More sophisticated researchers consider why there is more amyloid in the brains of Alzheimer's patients, and the elderly in general, and how that comes about and how it might be prevented. For example the SENS research program includes periodic removal of all amyloids as a goal because the presence of amyloid is a fundamental difference between old and young tissue, and therefore should be eliminated as a part of any repair-based rejuvenation treatment.
No consensus goes unchallenged in medical science, however, and there are a range of alternative views and proposed mechanisms for the harm caused by Alzheimer's disease, some of which add to the amyloid viewpoint as this one does. That there is further damage caused by amyloid that is not restored by simply removing the amyloid deposits is an incentive to develop periodic amyloid clearance treatments. These should be applied to healthy people throughout life, so as to prevent amyloid ever rising to the level at which it causes these further harms. All too much of the research community remains entirely committed to the model of waiting until the late stages of disease and then trying to repair everything that goes wrong at that time, however.
[This] research was motivated by the recent failure in clinical trials of once-promising Alzheimer's drugs being developed by large pharmaceutical companies. "Billions of dollars were invested in years of research leading up to the clinical trials of those Alzheimer's drugs, but they failed the test after they unexpectedly worsened the patients' symptoms." The research behind those drugs had targeted the long-recognized feature of Alzheimer's patients' brains: the sticky buildup of the amyloid protein known as plaques, which can cause neurons in the brain to die. "The research of our lab and others now has focused on finding new drug targets and on developing new approaches for diagnosing and treating Alzheimer's disease."
[The] research team found the neurotransmitter, called GABA (gamma-aminobutyric acid), in deformed cells called "reactive astrocytes" in a structure in the core of the brain called the dentate gyrus. This structure is the gateway to the hippocampus, an area of the brain that is critical for learning and memory. "Our studies of AD mice showed that the high concentration of the GABA neurotransmitter in the reactive astrocytes of the dentate gyrus correlates with the animals' poor performance on tests of learning and memory."
The high concentration of the GABA neurotransmitter in the reactive astrocytes is released through an astrocyte-specific GABA transporter, a novel drug target found in this study, to enhance GABA inhibition in the dentate gyrus. With too much inhibitory GABA neurotransmitter, the neurons in the dentate gyrus are not fired up like they normally would be when a healthy person is learning something new or remembering something already learned.
"After we inhibited the astrocytic GABA transporter to reduce GABA inhibition in the brains of the AD mice, we found that they showed better memory capability than the control AD mice. We are very excited and encouraged by this result because it might explain why previous clinical trials failed by targeting amyloid plaques alone. One possible explanation is that while amyloid plaques may be reduced by targeting amyloid proteins, the other downstream alterations triggered by amyloid deposits, such as the excessive GABA inhibition discovered in our study, cannot be corrected by targeting amyloid proteins alone."