Researching Alzheimer's disease using multiphoton microscopy to observe, in vivo, the anatomy and physiology of specific cell type in the brain.Our laboratory uses sophisticated optical techniques to address fundamental questions in Alzheimer's disease research. Using the imaging technique multiphoton microscopy, the senile plaques of Alzheimer's disease can be detected in the brains of living transgenic mice, and characterized with chronic imaging. This allows direct observation of the natural history of this deleterious pathological event in the brain.  In vivo imaging is also being used to characterize therapeutic approaches to clearing the senile plaques.  Current research is aimed at optimizing anti-amyloid treatments, and imaging the anatomy and physiology of specific cell types in the brain before and after treatment. We have implemented a variety of structural and functional fluorescent readouts that can be imaged at a variety of time-scales in the living brain of the mouse models of neurodegeneration.  Development of novel high resolution optical techniques is ongoing, and includes methods to measure and quantitatively analyze protein-protein interactions using fluorescence lifetime imaging microscopy (FLIM).  We are also developing non-invasive approaches to amyloid imaging in intact animals that should ultimately translate to the clinic.  This approach is truly multidisciplinary and involves active collaborations with chemists, physicists, and neurologists.  While the goals of my research are related to answering specific questions about Alzheimer’s disease, the techniques are broadly applicable to other biological problems. We continuously develop and validate fluorescent reporters to address a broad range of cellular and molecular targets with the goal of identifying therapeutic targets that will lead to clinically relevant treatments in humans.

Selected Publications:

Kumar AT, Skoch J, Bacskai BJ, Boas DA, Dunn AK.  Fluorescence-lifetime-based tomography for turbid media. Opt Lett. 2005 Dec 15;30(24):3347-9. 

Robbins EM, Betensky RA, Domnitz SB, Purcell SM, Garcia-Alloza M, Greenberg C, Rebeck GW, Hyman BT, Greenberg SM, Frosch MP, Bacskai BJ.  Kinetics of cerebral amyloid angiopathy progression in a transgenic mouse model of Alzheimer disease. J Neurosci. 2006 Jan 11;26(2):365-71.

Raymond SB, Skoch J, Hynynen K, Bacskai BJ.  Multiphoton imaging of ultrasound/Optison mediated cerebrovascular effects in vivo. J Cereb Blood Flow Metab. 2006 May 10.