The question of whether removing amyloid-β from the brain is therapeutic has been raised again by the recent interruption of the Elan/AHP trial due to clinical signs of inflammation. The rush to find a cure for this devastating disease has resulted in the complete neglect of over 15 papers in the literature that indicate amyloid-β has properties consistent with neuroprotective functions (reviewed in Atwood et al., 2001). These properties include metal chelation, antioxidant activity, and perhaps most importantly in the present context, sealant properties that we believe are involved in maintaining the structural integrity of the blood brain barrier and parenchymal structures (Atwood et al., 1998).

In keeping with the proposed role of amyloid-β as a metal chelating antioxidant and molecule involved in maintaining structural integrity under stress conditions, amyloid-β binds Cu under acidotic conditions and possesses hydrophobic and hydrophilic regions that span the plasma membrane and binds to extracellular matrix molecules (Atwood et al., 1998; Chan et al., 1999). These properties, together with its small size and ability to aggregate under inflammatory conditions makes amyloid-β an excellent candidate molecule that could form an intracranial “scab.” Cu, Zn aggregated amyloid-β would serve as a superoxide scavenging solid-phase matrix (Chan et al., 1999), which disassembles when Cu and Zn levels lower as tissue damage resolves (see Pluta et al., 1999). This may explain the acute phase generation and rapid cortical deposition of amyloid-β in stroke and following head trauma (Roberts et al., 1994), an important physiological response that would limit the loss of terminally differentiated neurons following head injury (Smith et al., 2000; Perry et al., 2000).