Alzheimerʹs Disease and Control Brain Contain Soluble Derivatives of the Amyloid Protein Precursor That End within the β Amyloid Protein Region

The 39-43 amino acid β amyloid protein (Aβ) that deposits as amyloid in the brains of patients with Alzheimerʹs disease (AD) is encoded as an internal sequence within a larger membrane-associated protein known as the amyloid protein precursor (APP). In cultured cells, the APP is normally cleaved within the Aβ to generate a large secreted derivative and a small membrane-associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire Aβ. Our study was designed to determine whether the soluble APP derivatives in human brain end within the β as described in cell culture or whether AD brain produces potentially amyloidogenic soluble derivatives that contain the entire β. We find that both AD and control brain contain nonamyloidogenic soluble derivatives that end at position 15 of the β. We have been unable to detect any soluble derivatives that contain the entire β in either the AD or control brain.