The projects listed below are designed to ask relevant questions about how Alzheimer's disease is identified, treated, and prevented. Each project has a unique goal and will contribute to our understanding of Alzheimer's disease. The projects are also described in this article, A Focus on the Future: Current ADRC Research Projects.
UW ADRC currently funded projects; UW ADRC funded pilot projects
Title: Cerebrospinal fluid (CSF) Proteome of Geriatric Dementia: CSF Protein Profiling of Central Nervous System (CNS) Insulin Activity
Project leader: Dr. Thomas Montine, Alvord Professor of Neuropathology, and Acting Chair, Department of Pathology at the University of Washington
Recent findings from small clinical trials suggest that clinically increasing the amount of insulin activity in the central nervous system may improve memory functioning in patients with amnestic mild cognitive impairment (MCI) or Alzheimer's disease. In this project, we aim to identify a set of cerebrospinal fluid (CSF) biomarkers that are responsive to changes in brain insulin activity in people with mild cognitive impairment or Alzheimer's disease. The project uses an advanced biological (or "proteomic") technique to examine the structures, functions, and changes of proteins that are present in the spinal fluid. We also hope to determine the significance of decreased brain insulin activity in age-related memory decline (i.e., occasionally misplacing items or having trouble retrieving names that are eventually remembered) and various forms of dementia. Finally, we will examine how insulin and cells relevant to Alzheimer's disease are concentrated in the brain by comparing the information discovered in this project to information obtained from previously collected brain tissue.
Title: Therapeutic Effects of Intra-Nasal Insulin Detemir
Project leader: Dr. Suzanne Craft, Professor, University of Washington, Department of Psychiatry and Behavioral Sciences
There is growing evidence that insulin is involved in multiple brain processes and that an impaired ability to control insulin can contribute to the development of Alzheimer's disease. As a result, therapies that attempt to restore the insulin levels in the central nervous system (CNS) may have beneficial effects on brain functioning. This project tests the therapeutic effects of nasally administered insulin with the hope that the insulin will improve memory and daily functioning in people with mild cognitive impairment (MCI) and Alzheimer's disease. To measure changes in spinal fluid biomarker levels, research participants will undergo lumbar punctures before insulin treatment and after the treatment has been completed.
Title: Modulation of Abeta Peptide Accumulation and Neuron Damage in Vivo with Adult Bone Marrow Transplants
Project leader: Dr. Christopher D. Keene, Assistant Professor, University of Washington, Department of Pathology, Division of Neuropathology
The ADRC has recently discovered that mice which have been genetically modified to have Alzheimer's disease have an approximately 50% reduction in beta-amyloid (find the definition here) after a "mini" bone marrow transplant. The 50% reduction in beta-amyloid is a significant finding because beta-amyloid is considered toxic to brain cells and may be responsible for some of the damage caused by Alzheimer's disease. Additionally, this limited version of a bone marrow transplant is less toxic to the body than the bone marrow transplants that are used to treat malignant diseases. This study draws upon these findings to conduct experiments that aim to increase our understanding of bone marrow transplants as potential treatments for Alzheimer's disease. The ADRC expects that our continued work with these mice will identify whether "mini" bone marrow transplants may help preserve brain functioning and will thereby lay the groundwork for potential treatments of Alzheimer's disease and other neurodegenerative diseases.
Currently Funded Pilot Projects
Health Education, Aerobic and Resistance Training (HEART) in Prediabetic African Americans
Project leader: Jeannine Skinner, PhD, UW Memory Wellness Center
Dr. Skinnner's project will compare the effects of exercise and health education on the thinking abilities, insulin sensitivity, and levels of Alzheimer's biomarkers in a group of African Americans with prediabetes.
Quantification of Abeta and tau in CSF by LC-MS/MS
Project leader: Andrew Hoofnagle, MD, PhD
This project aims to develop a new type of biomarker analysis to help translate already-known Alzheimer's biomarkers into practical, day-to-day diagnostic tests that can be reliably used in caring for people with Alzheimer's.
Preclinical Study of D2 Antagonists for Neuroprotection Against Pathological Tau
Project leader: Brian Kraemer, PhD
Dr. Kraemer's project studies a compound (D2 antagonists) to see if it is able to lessen tau development and toxicity through an animal model of Alzheimer's disease.
Neuroimaging Biomakers of Cognitive Resilience Among APOE-4 Carriers
Project leader: Tara Madhyastha, PhD
The goal of this pilot study is to identify neuroimaging biomarkers associated with memory change in midlife that my represent a preclinical phase of Alzheimer's disease.