There are approximately 100 distinct types of neurons in the human brain whose function is to communicate messages rapidly and precisely with other cells. One characteristic that defines these cells is whether or not they are classified as excitatory or inhibitory. An excitatory neuron increases the likelihood that an action potential—critical in cell-to-cell communication—will fire, whereas inhibitory neurons dampen neural activity. Excitatory neurons are more likely to be impaired in early Alzheimer’s disease, but the reason for the vulnerability has not been known. 

A new study shows that excitatory neurons are more susceptible to neurodegeneration; this study includes data indicating that tau accumulates selectively in excitatory neurons leading to increased vulnerability to Alzheimer’s disease in these cells. One of the genes identified is called BAG3. BAG3 is known to regulate the process by which the cell removes waste products. Reducing levels of BAG3 in neurons led to increased accumulation of tau; conversely, increasing levels of BAG3 protected neurons from tau. This study provides crucial evidence for the underlying cellular processes contributing to selective vulnerability of different neurons to tau pathology. 

Karen Duff, Ph.D., Columbia University