Defining a Role for the MS4A Genes in Alzheimer’s Disease

Alzheimer’s disease (AD) is caused by progressive changes in brain cells that culminate in memory loss, confusion, difficulty completing tasks, withdrawal, mood changes and, ultimately, death. The main cell type affected in the brain by Alzheimer’s disease is called the neuron, which is primarily responsible for processing information and generating action. Alzheimer’s disease damages neurons and the connections between neurons required to pass information along; as the ability of the brain to process information declines, so does the ability to care for one’s self and to interact with loved ones. One set of genes implicated in AD are the MS4A genes, which have a surprising degree of influence on a given person’s chances of getting Alzheimer’s disease later in life. We have developed preliminary data suggesting that mutation of Ms4a genes protects against late stages of AD, and that the way the MS4A genes influence the risk of getting AD relates to its impact on the immune system, both within the brain and in peripheral tissues like the blood, bone marrow and spleen. Here, we propose experiments to validate and extend these initial observations, which—if true—would suggest an important new strategy for combating neurodegeneration.