Analysis and Diagnosis of Alzheimer’s Disease Through the Development of Purification System of Biomarker and its Specific Peptide Probe

Abstract

Alzheimer’s disease (AD) is the most common type of dementia. AD cause memory loss, cognitive and physical impairments and finally death. Because this degenerative disease worsens slowly and gradually without knowing, the AD patients can notice the disease only after the disease is already advanced. There are no medications specifically used to cure the AD yet. Improving symptom control is the best way for all patients with advanced incurable AD. For this reason, early diagnosis is very important in treating AD. Amyloid beta 42 (Aβ42) is known for main hallmarks of AD pathogenesis. Aβ42 is overproduced and transform to amyloid aggregates such as oligomer, fibril and plaque in the brain of AD patient. As Aβ42 is accumulated, the neuronal cells undergo apoptosis affected by toxicity of aggregates. The concentration of Aβ42 in fluids of body such as CSF and blood is also changed due to its accumulation in the brain. For analysis of Aβ42 in brain, small sized peptide probes were screened towards recombinant Aβ42. Two different peptide probe were developed through two kinds of phage display. Each peptide showed strong binding affinity on micro molar range specifically and effectively detected Aβ42 in brain lysate via western blotting and probed Aβ42 in brian tissue via tissue staining. The concentration of Aβ42 in CSF was also estimated using peptide probe based diagnostic method. The peptide was screened towards monomer state of Aβ42. The developed diagnostic method could distinguish the amyloid positive patients by estimating the concentration of Aβ42 in CSF. In here, purification system of recombinant protein was constructed. Purified protein showed bioactivity assembling into taggregates like natural Aβ42. And specific peptide probes were screened towards Aβ42. They showed specific bindings and potentials in using as diagnostic agents. We anticipate that these research can be helpful to many other AD research.