A study of discovery, identification, and measurement of brain Aβ-like peptide;changes in the Aβ production process may generally be involved Alzheimer disease

Masayasu Okochi, Shinji Tagami, Masatoshi Takeda

Department of Psychiatry, Osaka University Graduate School of Medicine

Because clinical trials of anti-Abeta compounds/antibodies have been unsuccessful, Abeta-Knock-out strategy/Abeta hypothesis has been under severe pressure. To support current strategy for developing disease-course modifying drugs, we, first, described merits and demerits of current animal models for Alzheimer disease, which produce extremely high levels of Abeta in the brain. Pathological gain of function of familial AD-associated mutants are generally considered to be an increase in the Abeta42 ratio. We mentioned the possibility that changes in the relative ratio of Abeta42 to total Abeta production may also occur in brains of sporadic Alzheimer patients including MCI stage. Although we have shown that CSF APL1beta28 is a surrogate marker for brain Abeta42 production, further studies are necessary to judge if generation or clearance of Abeta42 is essential for formation of Abeta42 accumulation. Finally, we commented on future tasks of research of Alzheimer disease etiology and clinical intervention in future.

Address correspondence to Dr. Masayasu Okochi, Department of Psychiatry, Osaka University Graduate School of Medicine (2-2 Yamadaoka, Suita, Osaka 565-0871, Japan)