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Development of a Monoclonal Antibody Specific for ß/A4 Amyloid in Alzheimer's Disease Brain for Application to In Vivo Imaging of Amyloid Angiopathy

From the Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts
Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
NeoRx Corp., Seattle, Washington
Mallinckrodt Medical, Inc., St. Louis, Missouri
Alzheimer Center, University Hospitals, Cleveland
Department of Neurology, Case Western Reserve University, Cleveland, Ohio

Correspondence: For reprints contact: Charles A. Marotta, MD, PhD, Department of Neuroscience and Department of Psychiatry and Human Behavior, Brown University, Box G-M 209, Providence, RI 02912.

ABSTRACT

We evaluated the efficacy of murine monoclonal antibodies (Mabs) targeted to ß/A4 amyloid for development of procedures for the in vivo identification of amyloid angiopathy (AA) in Alzheimer's disease (AD). Mabs to ß/A4 amyloid were prepared and screened for effectiveness in visualizing AA and senile plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with ^99mTc using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity towards amyloid laden blood vessels and senile plaques. A highly specific murine Mab, 10H3, was identified and characterized that fulfills criteria necessary for the development of a diagnostic imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD.

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