Ada Locke Rose Hills
The role of inflammatory signaling and blood brain barrier degradation in cognitive decline
As we age, the protective barrier that separates circulating blood from neural tissue loses efficacy. Breakdown in this blood-brain barrier leads to excitatory synaptic remodeling, epileptoform activity, and, we hypothesize, cognitive dysfunction as seen in Alzheimers disease and dementia pathologies. The protein albumin in the blood is normally separated from brain tissue, but binds to TGF- receptors on astrocytes when the blood-brain barrier is compromised. This leads to an inflammatory signaling cascade and a host of changes in neural tissue that may contribute to cognitive decline. In our research, we seek whether application of IPW-5371, a novel TGF- receptor kinase antagonist, will lead to the reversal of inflammatory signaling and cognitive decline in aged mice and mice prematurely exposed to albumin, in hopes to reverse and prevent the onset of Alzheimers disease pathology.