Modified Project Summary/Abstract Section Alzheimer's disease (AD) is the most common form of neurodegenerative disorder associated with aging. One of the hallmarks of this disorder is the progressive loss of neuronal cells, which ultimately becomes fatal. Several lines of investigations implicate the role of vascular dysfunction, characterized by the loss of mural cells (pericytes) and compromised blood-brain-barrier, in pathogenesis of AD. Academic collaborators and founders of AivoCode Inc., the applicant company, have employed unbiased screening with in vivo phage display to probe specific vascular signature present in the brains of transgenic AD mice. This new approach to AD studies has generated a new and understudied therapeutic target, connective tissue growth factor (CTGF). CTGF binds extracellular matrices and cell surfaces including brain vasculature in AD mice. In this Phase I application, we propose to screen single domain antibodies against CTGF to neutralize CTGF activity in vitro and test CTGF targeting of these nanobodies in mouse models of AD. The results of this study will serve as stepping-stone for the company to develop a therapeutic candidate for AD.