Keith Johnson, M.D., leads the ACTC PET Imaging Unit, and is a Professor of Radiology at Harvard Medical School and Director of Molecular Neuroimaging in the Department of Radiology at Massachusetts General Hospital. Dr. Johnson has extensive experience in imaging research in neurodegenerative diseases, is a PI of the Harvard Aging Brain Study, and oversees the brain PET imaging program at MGH, which includes active research programs in imaging of amyloid-beta and PHF tau. Dr. Johnson leads the PET component of the A4 Study, as well as several other AD clinical trials. In addition, Dr. Johnson is a practicing Neurologist, Associate Physician in Neurology at Massachusetts General Hospital, and Associate Neurologist in the Division of Cognitive and Behavioral Neurology at Brigham and Women’s Hospital. He oversees the Clinical Brain PET Service at the MGH.

Dr. Hyman serves as Co-Lead for the ACTC Neuropathology Unit, and serves on the Project Evaluation Committee (PEC).  He is the John B. Penney, Jr. Professor of Neurology at Harvard University.  His laboratory studies the anatomical and molecular basis of dementia in Alzheimer’s disease and dementia with Lewy bodies. Approaches focus on transgenic mouse models and human neuropathological samples, using advanced microscopy techniques for in vivo longitudinal imaging, direct imaging on neuropathological processes including cell death, and functional imaging including in vivo assessment of calcium reporters. Quantitative approaches have been developed to apply to clinical pathological and genotype/phenotype analyses. Recent studies have developed the use of multiphoton microscopy for in vivo anatomical and functional imaging in transgenic mouse models of Alzheimer’s disease and the utilization of gene transfer techniques to introduce potentially disease-modifying genes into specific cortical regions. We have also developed fluorescence resonance energy transfer (FRET) approaches to allow observation of protein-protein interactions with subcellular resolution, both in vitro and in vivo. These techniques are utilized to examine the alterations that occur in Alzheimer’s disease brain, and in mouse models expressing genetic mutants that are linked to Alzheimer’s disease.

Rema Raman, PhD, is a tenured Professor of Neurology at the Keck School of Medicine of the University of Southern California (USC), the Director of Biostatistics of USC’s Alzheimer’s Therapeutic Research Institute (ATRI), and the Director of the Biostatistics Unit for the Alzheimer’s Clinical Trials Consortium (ACTC).   Dr. Raman also serves as Co-Lead for the ACTC Recruitment Unit and Co-Chair of the Inclusion, Diversity and Education in Alzheimer’s disease – Clinical Trials (IDEA-CT) Committee.  She is also Co-Chair of the Project Feasibility Committee.

Dr. Raman received her training in biostatistics from the School of Public Health at the University of Illinois at Chicago. Her statistical research interests are in efficient clinical trial design and monitoring approaches (risk-based monitoring, data visualization), and correlated data analysis topics (impact of missing data, analysis of ordinal data). Dr. Raman has extensive experience as a biostatistician in biomedical research projects, providing biostatistics and data management leadership to the design, coordination, conduct and analyses of clinical trials and large observational studies. She has served or currently serves as the primary statistician for several, multi-center clinical trials in Alzheimer’s disease, acute stroke, post-traumatic stress disorder, and traumatic brain injury. She is a regular member of the NIH CNN study section, an ad-hoc member on several others and serves as the Biostatistician on several Data and Safety Monitoring Boards.

Dr. Frosch serves as Co-Lead for the ACTC Neuropathology Unit.  He is the Lawrence J. Henderson Associate Professor of Pathology and
Health Sciences & Technology at Harvard Medical School, and Director of the C.S. Kubik Laboratory for Neuropathology at Massachusetts General Hospital, for the MassGeneral Institute for Neurodegenerative Diseases (MIND)

Dr. Frosch’s lab aims to understand cerebral amyloid angiopathy (CAA), using mouse models and human tissue. In this disease, the peptide Ab deposits in the walls of blood vessels and is associated with risk of hemorrhage (“lobar hemorrhages”). This peptide is the same material that forms the plaques of Alzheimer disease, and nearly all patients with Alzheimer disease have pathologic evidence of CAA as well. CAA also occurs in the absence of histologic  evidence of Alzheimer disease, and can present with hemorrhages or with cognitive changes.  In clinicopathologic studies, his lab has found that this latter presentation is associated with the presence of an inflammatory response, often containing giant cells. This subset of patients can have dramatic recoveries of cognitive function after immunosuppressive therapy.

Dr. Frosch and his team are interested in the sequence of events by which Ab is deposited in blood vessels, what factors determine the distribution of involvement, what the consequences are for the cells of the vessel and how this material can respond to therapeutic interventions focused on Ab currently in clinical trials. For in vivo studies, Frosch’s team uses serial multiphoton imaging with specific probes for these various processes and link the spatial and temporal distribution of the pathologic changes with the development of CAA. They complement these studies with work on human autopsy tissue, collected through the Massachusetts Alzheimer Disease Research Center Neuropathology Core. Those samples are examined through combinations of high field ex vivo MRI, optical clearing and volumetric imaging. They are particularly interested in the changes which result in bleeding in the setting of CAA (hemorrhagic strokes) as well as microinfarcts which can markedly impair cognition.

Dr. Frosch also works with a range of collaborators to understand the relationship between neuropathologic findings in the setting of disease — including Alzheimer disease, Parkinson disease, Amyotrophic Lateral Sclerosis and others — and other biochemical or functional markers of disease. These studies include advancing imaging methods (DTI, OCT and others) as well as various genetic studies (deep sequencing as well as GWAS), cell biology and structural biology.

Adam L. Boxer, MD, PhD is the Endowed Professor in Memory and Aging in the Department of Neurology at the University of California, San Francisco (UCSF).  He co-chairs the ACTC Non-Alzheimer’s Dementia Committee.  At UCSF, he directs the Neurosciences Clinical Research Unit and the Alzheimer’s Disease and Frontotemporal Degeneration (FTD) Clinical Trials Program at the UCSF Memory and Aging Center.  Dr. Boxer’s research is focused on developing new treatments and biomarkers for neurodegenerative diseases, particularly those involving tau and TDP-43.  He is the Principal Investigator of the Advancing Research and Treatment for FTLD (ARTFL) Rare Disease Clinical Research Consortium, a collaborative project funded by the National Institutes of Health to create an 18 center North American research network to support the development of new therapies for FTLD. He also leads the Four Repeat Tauopathy Neuroimaging Initiative (4RTNI), a multicenter, longitudinal tau PET and biomarker study focused on PSP and CBD.  He has been the PI for a variety of multicenter, randomized, placebo controlled clinical trials in FTLD spectrum disorders, including memantine for FTLD, davunetide for PSP, TPI-287 for primary and secondary tauopathies, and salsalate for PSP.  He co-chairs the FTLD Treatment Study Group (FTSG) and the PSP Research Roundtable, academic-industry collaborative groups working to speed the development of new therapies for FTLD, CBD and PSP.

Jason Karlawish is a Professor of Medicine, Medical Ethics and Health Policy, and Neurology at Penn and cares for patients at the Penn Memory Center (www.pennmemorycenter.org), which he co-directs. He leads the ACTC Ethics Committee, is a member of the Recruitment and Retention Core and the Steering Committee. At Penn, he leads the Outreach and Recruitment Core and Research Education Component of the ADRC. His research focuses on issues at the intersections of bioethics, aging and the neurosciences. He leads the Penn Program for Precision Medicine for the Brain (P3MB). P3MB developed standards for Alzheimer’s disease biomarker disclosure and investigates the clinical impacts of this knowledge on persons and their families. He has investigated the development and translation of Alzheimer’s disease treatments and biomarker-based diagnostics, informed consent, quality of life, research and treatment decision making, and voting by persons with cognitive impairment and residents of long term care facilities.  P3MB developed the amyloid imaging disclosure process and the SOKRATES Study, originally used in the A4 Study, these have become a template for assuring the safe disclosure of Alzheimer’s disease genes and biomarkers and assessing their impact on persons and their families.