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Spectroscopic Markers of Neurodegenerative Disease

(Developmental Collaborator-Driven Research Project)

UC Davis: J Brunberg, P Hagerman, D. Krol, S Wachsman-Hogiu, D. Garcia-Arocena, T Moritz

LLNL: J Chan

This work aims to develop and utilize spectroscopic tools to detect the optical signatures of proteins that are associated with specific degenerative neurological diseases, including Alzheimer’s disease (AD) and the fragile X-associated tremor/ataxia syndrome (FXTAS). These tools will on the near term help in studying and understanding these diseases and may in the long term improve the early non-invasive in vivo diagnosis and management of these disorders.

The definitive diagnosis of neurodegenerative disorders can involve invasive biopsy and subsequent tissue analysis.  The study of these disorders, in tissue and in cell culture, is generally destructive (e.g. fixation, fluorescent labels).  Alzheimer’s disease, for example, requires brain tissue histologic analysis to establish a definitive diagnosis. Raman spectroscopy and imaging of the neurodegenerative associated proteins would allow biochemical analysis of tissue samples and in vivo analysis of cell cultures without the need for fixation and labeling.

Project goals include: (1) Apply Raman spectroscopy and imaging to individual cells, and to animal and human tissue down to sub-cellular resolution using techniques such as micro-Raman, laser-trap Raman, temporal gating, and CARS techniques; (2) Identify unique optical signatures of these disorders; (3) Correlate Raman data with standard tissue histopathology techniques; (4) Develop these techniques for the in vivo non-invasive diagnosis and management of clinical neurodegenerative disorders.

We are the first group to obtain Raman spectra identifying inclusions from FXTAS cell cultures. These spectral signatures will allow for the first time (see figure) the identification and imaging of these inclusions within living cultured cells.