ABSTRACT
Alzheimer’s disease (AD) is the major cause o f dementia and the most com m on form o f human amyloidosis. AD affects an astoundingly large number of people and is common w ith advancing age. T he brains o f A lzheim er’s patients are typically riddled w ith insoluble ‘plaques” which consist o f amyloid. The major constituent o f brain and cerebrovas cular amyloid is amyloid-ß peptide (Aß). A num ber o f genetic, cell biology, biochemical and animal studies support the concept that Aß is central to AD. Here, we discuss regulation o f brain Aß and propose that amyloidosis in AD is a “storage” disease caused by inefficient trans port o f this peptide out o f the central nervous system. Thus, we suggest that sporadic AD is at least, in part, a clearance disorder due to defects in transport o f Aß that is produced at normal levels throughout the lifetime. The im portance o f transport-based clearance strategies in con junction with other Aß-lowering therapies (e.g., im munization/vaccination, Aß sequestering agents) in preventing the development o f cerebral ß-amyloidosis and/or clearing toxic clumps from AD brains is discussed.
