Generation of Rabbit Monoclonal Antibody to Amyloid-β 38 (Aβ 38 ): Increased Plasma Aβ 38 Levels in Down Syndrome

Abstract

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.