Generation of Rabbit Monoclonal Antibody to Amyloid-β38 (Aβ38): Increased Plasma Aβ38 Levels in Down Syndrome.

Abstract

Secreted soluble amyloid-β (Aβ)38 is the second most prominent Aβ form next to Aβ40, and is found in cerebrospinal fluid (CSF) and blood. Recent studies have shown the importance of quantitation of CSF Aβ38 levels in combination with those of Aβ40 and Aβ42 to support the diagnosis of Alzheimer's disease (AD), and other neurodegenerative diseases, and to facilitate drug discovery studies. However, the availability of reliable and specific Aβ38 monoclonal antibody is limited. Our first aim was to generate and partially characterize rabbit monoclonal antibody (RabmAb) to Aβ38. The antibody was specific to Aβ38, since it did not react with Aβ37, Aβ39, Aβ40, or Aβ42 in ELISA or immunoblotting. The antibody was sensitive enough to measure Aβ38 levels in plasma. Our second aim was to quantitate Aβ38 levels in plasma from older Down syndrome (DS) persons and age-matched controls. Persons with DS (35 years and older) have neuropathological changes characteristic of AD. Studies have shown that plasma Aβ40 and Aβ42 levels are higher in older persons with DS than in controls. However, none examined Aβ38 levels in DS. Our quantitation data showed that, like Aβ40 and Aβ42 plasma levels, Aβ38 plasma levels were higher in DS than in controls. Longitudinal studies will determine whether plasma Aβ38 levels in combination with levels of Aβ40 and Aβ42 are useful to predict early signs of AD in DS.