Heads of Laboratories
Vice President for Educational Affairs
Dean of Graduate and Postgraduate Studies
Patricia and John Rosenwald Laboratory of Neurobiology and Genetics
The brain is critically dependent on sufficient blood flow. Dr. Strickland’s laboratory investigates how dysfunction of the circulatory system contributes to neurological diseases, such as Alzheimer’s disease, in humans and mice.
Neurological disorders of the central nervous system represent profound medical problems worldwide. For example, Alzheimer’s disease affects millions of people and has severe physical, psychological, and financial consequences. By studying patients and mouse models with neurological diseases, Dr. Strickland is working to elucidate the molecular mechanisms by which neural function is disrupted.
In investigating neurovascular dysfunction, the Strickland lab studies the mechanisms underlying the pathogenesis of Alzheimer’s disease. Cerebrovascular defects contribute to the progression of Alzheimer’s pathology, and members of the lab are using transgenic mouse models of Alzheimer’s to evaluate blood-brain barrier damage and the roles that blood clot formation and degradation play in this disease. Their research has determined that the amyloid-β peptide, which is considered to be a causative factor in Alzheimer’s, interacts with fibrinogen to promote irregular fibrin accumulation in the brain and increase brain inflammation. This peptide also hinders blood clot degradation, which could compromise blood flow, exacerbate inflammation, and lead to neuronal death. These results suggest that fibrin and the mechanisms involved in its accumulation and clearance may present novel therapeutic targets for slowing the progression of Alzheimer’s disease.
The Strickland lab has also recently found that amyloid-β can activate coagulation Factor XII (FXII) in the plasma of both Alzheimer’s disease patients and mouse models. The activation of FXII initiates fibrin clotting as well as inflammatory processes, both of which are recognized pathologies in Alzheimer’s disease. Promotion of FXII activation by amyloid-β could help explain the association between Alzheimer’s disease and vascular diseases. This knowledge may ultimately identify new pathogenic mechanisms that could disrupt neuronal function, aiding in the discovery of novel diagnostic and therapeutic approaches.
B.S. in chemistry, 1968
Ph.D. in biochemistry, 1972
University of Michigan
The Rockefeller University, 1973–1975
Assistant Professor, 1975–1980
Associate Professor, 1980–1982
The Rockefeller University
Associate Professor, 1983–1987
State University of New York at Stony Brook
Dean and Vice President for Educational Affairs, 2000–
The Rockefeller University
John Simon Guggenheim Memorial Foundation Fellow, 1998
Innovative Research Award, Alzheimer’s Drug Discovery Foundation, 2009
Kruyer, A. et al. Chronic hypertension leads to neurodegeneration in the TgSwDI mouse model of Alzheimer’s disease. Hypertension 66, 175–182 (2015).
Zamolodchikov, D. et al. Activation of the factor XII-driven contact system in Alzheimer’s disease patient and mouse model plasma. Proc. Natl. Acad. Sci. U.S.A. 112, 4068–4073 (2015).
Cortes-Canteli, M. et al. Fibrin deposited in the Alzheimer’s disease brain promotes neuronal degeneration. Neurobiol. Aging 36, 608–617 (2015).
Ahn, H.J. et al. A novel Aβ-fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer’s disease mice. J. Exp. Med. 211, 1049–1062 (2014).
Hultman, K. et al. The APOE ε4/ε4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer’s disease patients. J. Cereb. Blood Flow Metab. 33, 1251–1258 (2013).