No abstract

We have identified a novel ␤ amyloid precursor protein (␤APP) mutation (V715M-␤APP770) that cosegregates with early-onset Alzheimer's disease (AD) in a pedigree. Unlike other familial AD-linked ␤APP mutations reported to date, overexpression of V715M-␤APP in human HEK293 cells and murine neurons reduces total A␤ production and increases the recovery of the physiologically secreted product, APP␣. V715M-␤APP significantly reduces A␤40 secretion without affecting A␤42 production in HEK293 cells. However, a marked increase in N-terminally truncated A␤ ending at position 42 (x-42A␤) is observed, whereas its counterpart x-40A␤ is not affected. These results suggest that, in some cases, familial AD may be associated with a reduction in the overall production of A␤ but may be caused by increased production of truncated forms of A␤ ending at the 42 position.

No abstract