Thesis (M.S.)--University of Michigan, 1990.

Thesis (M.Sc.). / Written for the Dept. of Neurology and Neurosurgery. Title from title page of PDF (viewed 2009/08/07). Includes bibliographical references.

Thesis (Ph. D.)--University of Virginia, 1997. / Spine title: Degenerative diseases of the CNS. Includes bibliographical references (250-259). Also available online through Digital Dissertations.

Thesis (M.S.)--University of Michigan, 1990.

Thesis (M.S.)--University of Michigan, 1996. / Includes bibliographical references.

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2005. / Not Embargoed. Vita. Bibliography: 182-204.

Thesis (Ph. D.)--Case Western Reserve University, 2005. / [School of Medicine] Department of Genetics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Embargoed. Vita. Bibliography: 168-212.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 93-102).

Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment (VAC+ENR) for 18 months. Learning and memory was evaluated throughout the study. Serum IgG antibody titers, cerebral spinal fluid (CSF) and brain Aβ were measured. Serum anti-Aβ1-42 IgG increased significantly in VAC animals. ENR but not VAC significantly increased CSF Aβ1-40. No cognitive improvements were observed in any group. VAC significantly reduced brain Aβ1-40 and 1-42, as well as reduced plaque load. An overall slowing of plaque accumulation was seen in the ENR group. VAC and ENR were able to modify pathology when used as separate treatments; however, the combination treatment did not succeed in further reducing Aβ or improving cognition. Previous AD clinical trials using immunotherapy yielded similar outcomes to our study showing reduced Aβ pathology but little to no cognitive improvements. In combination these results suggest that future studies should focus on prevention approaches both in the canine model and in human clinical trials.