Pharmacological Sciences

Cerebrovascular pathology in Alzheimer’s disease and related
disorders

Ph.D., Biochemistry, University of California, 1985

We are interested in understanding the role of amyloid ß-protein precursor
(AßPP) and its derived fragment Aß in the cerebrovascular pathology
found in Alzheimer’s disease and related disorders. Our research focuses
on pathogenic interactions of Aß with cells in cerebral blood vessels
that lead to cellular degeneration, loss of vessel wall integrity, and hemorrhagic
stroke. Our studies in this area are multi-leveled involving basic protein-protein
interactions, in vitro cerebrovascular cell culture models, and several in vivo
transgenic mouse models recently developed in the laboratory. In addition, we
have a strong interest in physiologic functions of AßPP in regulating
hemostatic mechanisms. To this end we utilize in vitro systems and several in
vivo mouse gene knockout and transgenic models to elucidate the role of AßPP
in vascular processes involved in coagulation, stroke, and traumatic brain injury.

Selected Publications

• Melchor, J.P. and Van Nostrand, W.E. (2000) Fibrillar Amyloid ß-Protein
  Mediates the Pathologic Accumulation of its Precursor in Cerebrovascular Smooth
  Muscle Cells. J. Biol. Chem. 275:9782-9791.
• Wagner, M.R., Keane, D.M., Melchor, J.P., Auspaker, K.R., and Van Nostrand.
  W.E. (2000) Fibrillar Amyloid ß-Protein Binds Protease Nexin-2/Amyloid
  ß-Protein Precursor: Stimulation of its Inhibition of Coagulation Factor
  XIa. Biochemistry 39:7420-7427.
• Van Nostrand, W.E., Melchor, J.P., Keane, D.M., Saporito-Irwin, S.M.,
  Romanov, G. Xu, F. and Davis, J. (2002) Localization of a Fibrillar Amyloid
  ß-Protein Binding Domain on its Precursor. J. Biol. Chem. 277:36392-36398.
• Jung, S.S., Zhang, W., and Van Nostrand, W.E. (2003) Pathogenic Aß
  Induces the Expression and Activation of Matrix Metalloproteinase-2 in Human
  Cerebrovascular Smooth Muscle Cells. J. Neurochem. 85:1208-1215.
• Davis, J., Wagner, M.R., Zhang, W., Xu, F., and Van Nostrand, W.E..
  Amyloid ß-Protein Stimulates the Expression of Urokinase-type Plasminogen
  Activator (uPA) and its Receptor (uPAR) in Human Cerebrovascular Smooth Muscle
  Cells. (2003) J. Biol. Chem. 278:19054-19061.