Scientists Say This Protein Might Help Combat The Effects Of Alzheimer's

There are a lot of ways that the anatomy of the brain might surprise you. In fact, the brain is the body part that eats itself and you never knew it. Recent research published in Alzheimer's & Dementia has also found that the cerebellum, which is crucial for long-term memory (not just motor skills and movement), plays an important role in Alzheimer's disease. As scientists continue to investigate this progressive disease, which causes deteriorating cognitive ability and memory, they've discovered a protein that could protect the brain from the damaging effects of toxic tau tangles.

The first hallmark of Alzheimer's is amyloid plaques that build up between nerve cells, and most research into understanding and treating the disease has focused on that. With approved treatments that target these plaques having disappointing results, research has started to steer toward the second hallmark: tau tangles. Tau is a naturally occurring protein that maintains nerve cell function and shape. When a chemical change twists it into toxic tangles, it can accumulate inside nerve cells, contributing to Alzheimer's.

New research published in Science Advances demonstrates that sorting-related receptor with A-type repeats (SORLA) — an intracellular protein — plays a protective role for nerve cells by hindering the generation and accumulation of amyloid-beta. While further investigating the protein's role in crossbred mice (those that produce a lot of human SORLA with those that develop tau tangles), they found that higher levels of SORLA interfere with the formation of tau tangles, prevent malformed tau from recruiting more tau, and slowed the degeneration of neurons. The same mice also had healthier neural connections (synapses) and better preserved synaptic plasticity (adaptive weakening or strengthening of synapses as necessary).

The discovery of SORLA's role in protecting the brain comes after scientists may have solved a long-standing Alzheimer's mystery involving how the protein Arc is critical for the transmission of tau tangles into nerve cells. However, why does SORLA work like it does? The researchers used multiple advanced mapping and sequencing methods to show the locations of proteins and RNA in the mice brain tissue while measuring gene activity and protein level in each cell.

When comparing the analysis between mice with high and low levels of SORLA, they found that increasing the protein actually suppressed harmful changes in the synapses' protein production and other biological pathways linked to the progression of Alzheimer's and other tauopathies. It also decreased gene activity known to occur with diseases in glial cells, which are cells that stabilize and support the function of nerve cells.

Now, the researchers plan to investigate the effects of increased SORLA levels on other brain cell types. Since cells differ between humans and mice, their plan to conduct a study in a living-disease-environment is expected to involve grafting human glial or neuron cells into the mice brains. They also want to clarify how the protein protects the brain and whether therapeutic treatment can enhance that protection. Since SORLA has an impact on amyloid and tau pathology, such a treatment could potentially address the broader biological process involved in Alzheimer's. Other researchers may be able to use these findings to repurpose existing drugs to treat the disease and other tau-driven dementias, too.