New Insights into How Amyloid-Beta Damages Brain Nerve Cell Communication in Alzheimer’s Disease Configure
What: Early research shows one can prevent loss of brain nerve cell communication in Alzheimer’s disease by blocking ‘caspase’ from making toxic amyloid-beta from APP.
Where: Park G, Nhan HS, Tyan SH, Kawakatsu Y, Zhang C, Navarro M, Koo EH. Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid β-Protein-Induced Synapse Loss in Alzheimer’s Disease. Cell Reports. 2020 Jun 30;31(13):107839 Read more about this research.
BrightFocus Connection: This project was supported by an Alzheimer’s Disease Research Postdoctoral Fellowship Award to publication first author Goonho Park, PhD, of the University of California at San Diego (Fellowship Mentor is publication last author, Dr. Edward Koo).
Why It Is Important: Amyloid plaque deposits have long been associated with neurodegeneration in Alzheimer’s disease (AD); however, the precise ways in which the toxic amyloid-beta damages neurons is still being explored. A part of it is thought to involve the loss of synapses, or the tiny connections between neurons. Synapses play an indispensable role in brain communications via the release and uptake of neurotransmitter signaling proteins, and dysfunction/loss of synapses is widely seen as a contributor to cognitive impairment. In new work supported by BrightFocus, Dr. Goonho Park shows how changing the ‘spelling’ of one ‘letter’ on the APP protein (the precursor ‘building block’ to creation of amyloid-beta), can prevent the caspase protein-driven cleavage (or breakage) into the toxic protein, thus saving the synaptic connections between cells. This discovery seems to further support the so-called “amyloid hypothesis” where it is thought that problems with amyloid-beta protein does directly impact cognition and brain function in AD. If the results of this research are further translated from cell and animal studies into clinical settings, these results could be very important in that they could offer a new AD treatment target to prevent such damage to brain cells and subsequent memory loss.