Fig. 7.

Schematic summary of DHCR24 knock-in reverses AD-related pathology and enhances cognitive ability of 5xFAD mice. To demonstrate the contribution of DHCR24 in improving the cognitive ability of AD, we employed delivery of adeno-associated virus (AAV) carrying DHCR24 gene into the hippocampus of 5xFAD mice. After DHCR24 transfection, DHCR24 is universally co-expressed in neurons and astrocytes, resulting in the increase of neuronal cholesterol level. By enhancing neuronal cholesterol level, DHCR24 knock-in successfully prevented or reversed AD-related pathology, including amyloid-β deposition, synaptic injuries, inhibition of autophagy, and apoptosis. Finally, DHCR24 knock-in obviously improved the cognitive ability of 5xFAD mice