We then moved to the PS19 mouse model of tauopathy to test if inhibition of BMP signaling would prevent some of the tau pathology and cognitive deficits seen in this model. With noggin over expression we were excited to see improvement in cognitive tasks and lower levels of tau pathology!

When treated with BMP4 ligand to activated the signaling cascade, tau phosphorylation increases (most significantly in APOE4 neurons !!!!). When treated with BMP antagonist, noggin, tau phosphorylation was almost completely preventing in AD neurons.

I used our APOE AD iPSC model to study both levels of BMP signaling in a genotypic manner, but also the correlation to tau phosphorylation. APOE4 neurons had a higher levels of BMPs at baseline compared to APOE4. This along with downstream effectors that relate to AD pathology (ie kinases).

Our lab has been studying BMP signaling in the context of development and aging for the past decade+. We have found that is is not only important for lineage commitment but as we age BMP signaling increases in the brain. I was interested to study BMP signaling in the context of neurodegeneration...