Targeting astrocytes with viral gene therapy for alzheimer’s disease

Alzheimer’s disease (AD), the leading cause of dementia worldwide, results from the accumulation of amyloid plaques within the brain parenchyma and the formation of neurofibrillary tangles within degenerating neurons. While neuronal degeneration is the major consequence of the disease, leading to memory loss, cognitive decline, and eventual death, other cell types within the central nervous system contribute to disease pathogenesis. In this chapter, we examine the essential role of astrocytes in normal brain physiology and in AD pathogenesis. Furthermore, we explore astrocyte-specific mechanisms that provide potential targets for intervention with novel viral gene transfer technologies that provide specific and efficient astrocyte transduction. Finally, we review several preclinical studies that illustrate the possibility that astrocytes can be selectively targeted to attenuate and potentially reverse disease progression.