Background: The presence of toxic soluble aggregates of two proteins, amyloid beta and tau, are indicative of Alzheimers disease. Following TBI there is a spike in concentrations of both amyloid beta and tau and also alpha-synuclein (a-syn) a protein correlated with Parkinsons disease. Detection of toxic aggregates of these proteins in CSF samples can be used as biomarkers for specific neurodegenerative diseases. Our lab has developed novel antibody fragments or nanobodies that selectively recognize toxic forms of these target proteins. Objective/Hypothesis Characterizing CSF levels of a key set of toxic biomarkers will provide a diagnostic tool for soldiers with early AD or increased susceptibility for AD following TBI. Our objective is to identify the set of CSF biomarkers that are diagnostic for AD and TBI patients that have increased risk of AD. Specific Aims: 1: Refine assay for detection of CSF biomarkers. 2: Determine concentrations of toxic amyloid beta, tau and a-syn species in CSF samples from TBI, cognitively normal (ND), and AD patients. 3. Identify biomarkers that distinguish AD, TBI and ND. 4: Generate additional nanobodies to tau species unique to TBI to include in the biomarker set. Study Design 1) Refine sandwich ELISA protocols for detecting of biomarkers in CSF samples using nanobodies. 2) Determine levels of six different toxic forms of beta-amyloid, a-syn tau in CSF samples of normal, AD and TBI patients. 3) Identify biomarkers indicative of AD and TBI. 4) Isolate additional nanobodies that specifically recognize tau species unique to AD and TBI. We will add these nanobodies to the sample set as they become available to provide additional biomarkers to help identify early AD cases. Relevance: An early diagnostic indicator for AD, and particularly of increased susceptibility to AD following TBI, is critically important to identify which soldiers have neuronal damage consistent with AD so treatment can begin early and the effectiveness of the treatments can be monitored.
|Effective start/end date||9/25/12 → 3/24/15|
- US Department of Defense (DOD): $339,424.00