Alzheimer’s disease (AD) robs people’s memories and destroys lives, but despite of almost daily reports on promising new therapies, AD still remains unchecked. The March 23 issue of the journal PLoS One reveals that a new study has discovered the mechanism that causes memory loss in AD, which could pave the way for new treatments.
The brains of AD patients commonly have two types of lesions; the beta-amyloid plaques outside neurons and the neurofibrillary tangles within the neurons. It is known that AD genes affect plaques, however, AD symptoms are more closely associated with tangles that consist of the “tau” protein, which is usually attached to microtubules; it is also known that excess beta-amyloid plaques induce tangles, disrupt microtubules, and cause memory loss, even with normal synaptic function, yet how this occurs is still not known.
According to scientists from Harvard, Boston University, The University of Alberta, The University of Arizona and The Chopra Foundation, AD memory loss is caused because of a disruption of microtubules due to zinc imbalance.
Senior researcher, Dr. Rudolph Tanzi from Harvard and his team demonstrated earlier that plaques outside neurons isolate zinc and decreasing the levels inside the neurons. Zinc is known to stabilize numerous protein complexes, such as microtubules (MTs), polymers of tubulin. MTs control synapses and were recently shown to have a key impact in memory encoding in neurons.
In the present study, Craddock and his team made three major discoveries. They discovered that specific zinc-tubulin binding sites promote side-to-side tubulin interactions, which are vital to MT polymer structure and demonstrated the method in which extra-neuronal zinc sequestration decreases intra-neuronal zinc available to tubulin, hence destabilizing MTs and leading to tangles by performing a kinetic analysis.
They also demonstrated that metallomic imaging mass spectrometry (MIMS) of AD model mice revealed abnormal zinc distribution in critical brain regions.
The findings indicate that therapies based on stabilizing MTs could normalize intra-neuronal zinc levels by administering zinc ionophore drugs like PBT2 (Prana Biotechnology) and promote MT self-assembly and stability by other drugs and through transcranial therapies, for instance through ultrasound at MT resonant frequencies in megahertz.
Tanzi, who is a leading Alzheimer’s expert concluded:
“It looks like beta-amyloid plaques themselves aren’t destructive directly, but lead to lower zinc levels within neurons. This in turn disrupts microtubules and tau, causing tangles and memory loss. Protecting microtubules and their association with tau may be the best treatment approach in Alzheimer’s disease.”
Written by Petra Rattue