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Oligomeric Neuronal Protein Aggregates as Biomarkers for Traumatic Brain Injury (TBI) and Alzheimer Disease (AD)

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Annual rept. 30 Sep 2012-29 Sep 2013

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Misfolding and aggregation of amyloid beta A and tau result in the hallmark pathological plaques and tangles associated with AD while aggregation of the protein alphasynuclein a-syn forms Lewy Bodies, the hallmark feature of Parkinson s disease. While large fibrillar aggregates of each of these proteins are diagnostic features of these diseases, increasing evidence indicates that smaller soluble oligomeric species of these proteins are key neurotoxins involved in the onset and progression of these neurodegenerative diseases. Since A , tau and a-syn all also accumulate in the brain following traumatic brain injury TBI, presence of selected toxic aggregate forms of these proteins can provide valuable early biomarkers for AD and other neurodegenerative diseases and identify specific neuronal damage in soldiers who have incurred traumatic brain injury TBI. Our lab has developed unique technology that enables us to isolate reagents that bind specific morphologies of a target protein. We have developed various recombinant antibody fragments, or nanobodies, that selectively recognize three different oligomeric A species, two different oligomeric asyn species, and one oligomeric tau species. This pool of six different morphology specific nanobody reagents represent a valuable tool to probe human CSF samples to identify biomarkers for early diagnosis of AD and to identify neuronal damage following TBI.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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