This episode presents a fascinating conversation with Dr. Orly Lazarov about her groundbreaking research on Alzheimer’s Disease (AD) and the pivotal role of hippocampal neurogenesis in memory deficits observed in this condition.

The recruitment of new, immature neurons into the memory "engram" or storage, which is essential for hippocampus-dependent tasks, is significantly deficient in familial Alzheimer’s Disease (FAD) cases. These recruited immature neurons exhibited compromised spine density and altered transcript profiles in FAD.

In a remarkable revelation, Dr. Lazarov’s team demonstrated that targeted enhancement of neurogenesis in FAD mice can restore the number of new neurons in the engram, along with the dendritic spine density and the transcription signature of both immature and mature neurons. This restoration leads to memory rescue. Additionally, the team found that chemogenetic inactivation of immature neurons reversed mouse performance and impaired memory.

Notably, AD-linked genes like App, ApoE, and Adam10 were among the top differentially expressed genes in the engram. Dr. Lazarov's study implies that defective neurogenesis contributes significantly to memory failure in Alzheimer's disease.

Join us as we delve into the complex world of neurogenesis, memory, and Alzheimer's disease with Dr. Lazarov.

Keywords: Alzheimer's Disease, Neurogenesis, Memory Failure, Hippocampus, Familial Alzheimer's Disease, Engram, Memory Rescue, Dendritic Spine Density.

Augmenting neurogenesis rescues memory impairments in Alzheimer’s disease by restoring the memory-storing neurons https://doi.org/10.1084/jem.20220391