Commercialization of a Diagnostic Test for Alzheimer's Disease

DESCRIPTION (provided by applicant): The major barriers to preventing or treating Alzheimer's disease (AD) are its unknown pathogenesis/etiology and the lack of an objective, sensitive and specific biomarker of the disease, particularly at the early stages when therapeutic interventions would likely have the greatest efficacy. The basic hypothesis of this project is that levels of a unique high molecular weight protein/protein complex consisting of 1 molecule of lipocalin (brain-specific) prostaglandin-d-synthase (PDS) and 1 dimer of transthyretin (TTR) quantified in cerebrospinal fluid (CSF) using an enzyme linked immunoassay (ELISA) developed and characterized by Scout Diagnostics will serve as an effective biomarker to identify Alzheimer's disease (AD) subjects early in disease progression. To convert the basic science developed during Phase I funding to a commercially viable product, we propose to: a). synthesize and purify authentic PDS/TTR complex using recombinant human proteins generated in our laboratory for use as a standard for ELISA calibration and quantification; b) evaluate product storage and shipping requirements and prepare a horseradish peroxidase labeled probe antibody to decrease analysis time and; c) prepare and field test an instruction manual for use in independent diagnostic laboratories. To more fully characterize the PDS/TTR ELISA, we propose to analyze CSF specimens from an additional 150 AD and 150 control subjects from three geographically distinct Alzheimer's disease centers (ADCs) and to carry out inter-laboratory validation studies by providing those ADCs with ELISA kits, instructions and representative CSF specimens for analysis of duplicate aliquots of the same samples in their laboratories. In addition, we will further determine the specificity of the biomarker for AD patients by analyzing CSF from 50 subjects with non-AD neurologic disorders including frontotemporal dementia, corticobasal degeneration and parasupranuclear palsy. Overall, our preliminary data suggest that use of the PDS/TTR complex either in CSF or in serum may provide an objective biomarker with sufficient sensitivity/specificity for the identification of AD subjects. PUBLIC HEALTH RELEVANCE: Alzheimer's disease (AD) is the fourth leading cause of death in the United States and currently affects 4.5 million Americans. Two major barriers to treating and eventually preventing AD are: 1) the lack of understanding about the process of neuron degeneration and loss and 2) the lack of a sensitive and specific biomarker of the disease. Preliminary and future studies described in this proposal show that a novel protein-protein complex present in cerebrospinal fluid can be quantified using an enzyme linked immunoassay (ELISA). This protein-protein complex is a sensitive and specific biomarker of AD including early stages of AD (mild cognitive impairment) when therapeutic interventions are most likely to have beneficial effects.