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Brian was  excited about macrophages/microglia as chassis idea.  Relevant paper: Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions

6/23/14

Microglia Lacking E Prostanoid Receptor Subtype 2 Have Enhanced AB Phagocytosis yet Lack AB-Activated Neurotoxicity
Deletion of the Prostaglandin E2 EP2 and phagocytosis of AB.pdfReceptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer’s Disease

The papers think EP2 could be a potential target for AD treatment.

EP2 potential target for AD. Knocking out EP2 increases phagocytosis of AB-immunoreactive material (hence, AB) by a LOT, and microglia lacking EP2 do not cause neurodegeneration. EP2 has been associated with other brain disorders and I could not find papers that show that . Detrimental effects of EP2-/- has detrimental effects on the brain (only thing I found: Salt−sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor), Neuroprotective Function of the PGE2EP2 Receptor in Cerebral Ischemia.
We could downregulate EP2 in microglia in response to AB (same as we are planning for BACE1 currently). The paper thinks EP2 could be a potential target for AD treatmentSince they will only be in microglia, the shouldn't cause problems with other cells. The system should shut down without AB signalling.