Excessive local host-graft connectivity in aged and amyloid-loaded brain

Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment in the host on transplant connectivity. To explore the influence of ageing and amyloid pathology in Alzheimer's disease (AD) we examined graft connectivity using monosynaptic Rabies virus tracing in APP/PS1 mice and in 16-18 month-old wild type mice. Neurons differentiated within 4 weeks and integrated well into the host visual cortex receiving input from the regions appropriate for visual cortex. Surprisingly, however, we found a prominent several-fold increase in local visual cortex input connectivity in both amyloid-loaded and aged environment. State-of-the-art deep proteome analysis using mass spectrometry provides first insights into the composition of environments promoting or not local exuberant input connectivity. These data therefore highlight the key role of the host pathology in shaping the input connectome calling for caution in extrapolating from one to another pathological condition.