Massachusetts General Hospital

Using With the mulitphoton micrsocopy imaging technique, senile plaques of Alzheimer's disease can be detected in the brains of living transgenic mice, and characterized with chronic imaging.

This detection platform was used to characterize a therapeutic approach to clearing the senile plaques based on immunotherapy, as well as to characterize novel amyloid-targeting ligands in preclinical development for PET imaging in humans.

Current research is aimed at optimizing anti-amyloid- therapeutic approaches, and imaging the anatomy and physiology of specific cell types in the brain before and after treatment. Development of novel optical techniques is ongoing, and includes methods to measure protein-protein interactions using fluorescence lifetime imaging microscopy (FLIM), and non-invasive approaches to amyloid imaging in intact animals.

Principal Investigator

Brian J. Bacskai, PhD

• Professor of Neurology,
  Harvard Medical School
• Principal Investigator, Neurology,
  Massachusetts General Hospital

Research Scientists

• Arbel, Michal, PhD - Post Doc Fellow
• Hou, Steven - Graduate student
• Kumar, Anand, PhD - Post Doc Fellow
• Raymond, Scott - Graduate student
• Xie, Hong, PhD - Post Doc Fellow

Research Assistants & Technicians

• Boivin, Josiah - Research Technician
• Neal, Krista - Research Technician
• Thyssen, Diana - Rearch Technician

Updated 03/29/2012

Serial in-vivo imaging of ceregral amyloid agiopathy (CAA) in a  Tg2576 mouse starting at 10.3 months.  The images shown are at the 4th, 5th and 6th week of imaging.  CAA deposition proceeds mostly through propagation of existing deposits.  Robbins et al.

Amyloid plaques alter the morphology and trajectory of neurites in-vivo.  GFP filled neurites (in green) curve around the plaque (blue, stained with methoxy-XO4, rather than penetrating the plaque.  The arrow indicates a distrophic neurite.  Blood vessels contain Texas Red Dextran.  Spires et al.

A FLIM pseudocolor representation of a senile plaque labeled with fluorescent 3d6 and 10d5 exhibiting flourescent energy transfer (FRET).  Lifetimes are not uniform throughout the plaque, but rather show a reduction at the periphery (red) as compared to the core (blue/green).  Bacskai et al.

F(ab)2 fragments of 3d6 are equally effective as full length 3d6 at clearing away diffuse amyloid.(green) after three days in the PDAPP mouse model.  Bacskai et al.

Dense core plaques activate the fluorogenic activator Amplex Red in-vivo (A).  Histochemical marker ThioFlavin-S confirms the presence of the dense core plaque (C).  McLellan et. al.

Imaging of an intact mouse brain from a 22 month Tg2576 mouse imaged after staining with ThioFlavin-S.  By 22 months, Tg2576 mice develop extensive CAA.  Domnitz et. al.

There are currently no open positions.

1. Elissa M. Robbins, Rebecca A. Betensky, Sarah B. Domnitz, Susan M. Purcell,  Monica Garcia-Alloza, Charles Greenberg, G. William Rebeck, Bradley T. Hyman, Steven M. Greenberg, Matthew P. Frosch, and Brian J. Bacskai. Kinetics of Cerebral Amyloid Angiopathy Progression in a Transgenic Mouse Model of Alzheimer Disease.   Jan. 2006.  Journal of Neuroscience
2. Kumar AT, Skoch J, Bacskai BJ, Boas DA, Dunn AK. Fluorescence-lifetime-based tomography for turbid media. Opt Lett. 2005 Dec.
3. Golde TE, Bacskai BJ. Bringing amyloid into focus. Nat Biotechnol. 2005 May
4. Skoch J, Dunn A, Hyman BT, Bacskai BJ. Development of an optical approach for noninvasive imaging of Alzheimer's disease pathology. J Biomed Opt. 2005 Jan-Feb
5. Garcia-Alloza M, Bacskai BJ. Techniques for brain imaging in vivo. Neuromolecular Med. 2004

MassGeneral Institute for Neurodegenerative Disease

Phone: 617-726-2000
Fax: 617-724-1480
Email: mghmind@partners.org

Public Transportation Access: yes
Disabled Access: yes

How to Apply for Positions

How to apply for jobs: Send an e-mail to mghmind-jobs@partners.org to receive an automated e-mail with full instructions for all types of positions.

Fundraising Contact

Contact Shawn Fitzgibbons in the Mass General Development office at 617-643-0447 or sfitzgibbons@partners.org.

Administration

Anne B. Young, MD, PhD
Director, Massgeneral Institute for Neurodegenerative Disease 
Professor of Neurology, Harvard Medical School

Directions to MIND Research labs (PDF)

Clinical Appointments, Consultations & Clinical Trials

Please visit the main Neurology Service Contact page for all other contact information.