Exogenous human beta amyloid peptide interferes osteogenesis through Sox9a in embryonic zebrafish.

The two major hallmarks of Alzheimer's disease (AD) are beta-amyloid plaques and neurofibrillary tangles. Amyloid peptide aggregations in the brain cause loss of synaptic connections and subsequent neurotoxicity leading to neurodegeneration and memory deficits. However, the physiological effects of beta-amyloid on early embryonic development still remain unclear. Administration of human beta-amyloid peptide (1-42) through cerebrospinal ventricular injection was carried out at 24 hpf (hours post fertilization) and it was uptaken into the cellular layers of the early ventricular development without any plaque aggregation. Whole-mount Immunostaining of zebrafish embryos injected with the beta-amyloid at 60 hpf revealed the delay in Sox9a expression. Decreased level of cartilage to bone transformation rate in 15 dpf (days post fertilization) zebrafish was observed by differential staining. These results suggest the possible existence of a genetic relationship between extrinsic amyloid peptide and Sox9a expression. Thus, our results demonstrated that the human beta-amyloid influences bone development through Sox9a expression during osteogenesis in zebrafish.