The research proposed here will lead to the development of a practical, non-invasive, comparatively inexpensive method for diagnosing Alzheimer's disease (AD) using near-infrared (NIR) low energy laser spectroscopy. AD is an ideal candidate for spectroscopic diagnosis. The demonstrated presence of unique biochemical markers (senile plaques containing amyloid fibrils and neurofibrillary tangles rich in phosphorylated proteins), will provide unique spectroscopic signatures. Researchers developing cerebral oxygen monitors and studying brain optical tomography have shown that brain tissue is highly translucent to NIR wavelengths and that sufficient light can be transmitted and detected through an intact adult skull for diagnostic purposes. The region of highest concentration of AD markers is the temporal lobe, located beneath the temple where the skull is thinnest. The laser energy used is safe, and the components needed to generate and detect these wavelengths are readily available. The device is intended for use at the bedside in order to measure the degree of disease, an essential capability for determining the efficacy of proposed curative treatments and monitoring disease progress. This proposal represents a collaboration between the MIT Laser Biomedical Research Center (LBRC), a leader in spectroscopic diagnostic research and the Bedford VA Medical Center (VAMC), a leader in AD research. LBRC has successfully demonstrated diagnosis of cancer in various organs using laser induced fluorescence (mouth, colon, bladder, breast), and quantitative biochemical classification of coronary artery blockages and blood analytes (glucose, albumin), using Raman scattering. Preliminary studies performed at the LBRC comparing specimens of normal and AD temporal cortex and temporal bone, provided by VAMC (including both microscopic and bulk samples), show very promising signatures in both fluorescence and Raman spectra. This work will establish the appropriate choices of signatures, wavelengths and algorithms needed to design a clinical system. In particular, a prospective study in vitro demonstrated near-infrared fluorescence spectroscopy detects AD in human brain tissue. This work will establish the appropriate choices of signatures, wavelengths and algorithms needed to design a clinical system.
