Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer’s Disease–Like Neuropathology in Tg2576 Mice

HCK deficiency in Tg2576 mice is associated with accelerated cognitive decline and elevated Aβ levels.

• Loss of HCK impairs microglial homeostasis and the clearance of amyloid-β (Aβ).
• Elevated Aβ levels and plaque burden were observed in HCK-deficient mice.
• Cognitive decline was accelerated in the absence of HCK.
• Microglial phagocytosis of Aβ was attenuated in mice lacking HCK.
• Increased expression of iNOS in microglial clusters was noted with HCK deficiency.
• Reduction of pre-synaptic protein levels occurred in hippocampal regions of HCK-deficient mice.

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