I would add that recent evidence from animal models of AD suggests the following:
1. At least part of the inflammatory response in AD is due to recruitment of blood/bone marrow-derived mononuclear phagocytes (monocytes and/or microglial precursors).
2. The early inflammatory response appears to be beneficial, in that it mediates the clearance of Aβ.
3. It is not clear at what stage of AD pathology the inflammatory response becomes detrimental, further contributing to neurotoxicity. Does the switch occur before formation of visible plaques? Is it due to soluble/oligomeric Aβ, or to fibrillar Aβ?
Simard AR, Soulet D, Gowing G, Julien JP, Rivest S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease.
Neuron. 2006 Feb 16;49(4):489-502.
Khoury JE, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease.
Nat Med. 2007 Mar 11; [Epub ahead of print]
View all comments by Joseph El Khoury