Microscope ImageAt the UW ADRC, we are busy trying to find ways to identify, treat, and prevent Alzheimer’s disease. We tackle these challenges through the ongoing work of our cores, through nationwide collaborative studies, and through the five-year projects and one-year pilot projects listed below, each of which attempts to contribute to our understanding of Alzheimer's disease in new and innovative ways.

UW ADRC currently funded projects; UW ADRC funded pilot projects

Project 1

Title: Mechanisms Linking Normative Aging with Alzheimer’s Disease
Project leader: Dr. Matt Kaeberlein,  Professor, Department of Pathology, University of Washington

Age is the single greatest risk factor for Alzheimer’s disease, yet the way in which normal aging processes differ from those processes that lead to Alzheimer’s isn’t entirely clear. This project seeks to understand the molecular processes that cause cells to become more susceptible to Alzheimer’s by studying aging roundworms known as nematode Caenorhabditis elegans (C. elegans). Using the nematode model, we will determine the effects of toxic amyloid-beta on gene expression in the context of normal aging. Then, we will explore how two important signaling pathways, the hypoxic response and the mechanistic target of rapamycin (mTOR), modulate cellular resistance to amyloid-beta toxicity. Previously, the Kaeberlein Lab has shown that both of the pathways regulate normal aging and resistance to amyloid-beta in C. elegans. These studies are likely to provide novel insights into the relationship between normal aging and AD with the overall aim of developing therapies that will delay the onset and progression of Alzheimer’s.

Project 2

Title: Rationally designed modulators of the amyloid-beta aggregation cascade
Project leader: Dr. David Baker, Professor, Department of Biochemistry, University of Washington, and Investigator, Howard Hughes Medical Institute

The accumulation of abnormally folded amyloid-beta proteins is widely accepted as the root cause of Alzheimer’s disease, but researchers have had difficulty developing medications that counteract these misfolded proteins. In this Project, we will use advanced computing techniques to design proteins and peptides that can alter these harmful processes, preventing the toxic amyloid-beta proteins from abnormally folding and accumulating in the brain. These artificially created peptides and proteins will be useful for developing new AD treatment strategies.

Project 3

Title: Standardized Brain Imaging, Spinal Fluid Analysis, and Cognitive Data Collection in ACT Subjects
Project leader: Dr. Thomas Grabowski, Professor, Departments of Radiology and Neurology, University of Washington, and Director, Integrated Brain Imaging Center, University of Washington

Imaging studies have identified altered functional connectivity in what is known as the default mode network (DMN) as a marker of preclinical Alzheimer’s disease. However, it is unclear how likely these changes are to predict Alzheimer’s-related memory decline, particularly in contrast to the dementia caused by cerebral microvascular disease as indicated by autopsy. Indeed, the Adult Changes in Thought (ACT) study, a community-based study of brain aging and incident dementia in the Seattle area, has demonstrated in large autopsy studies that the population-attributable risk of dementia in ACT was 45% from AD and 33% from cerebral microvascular disease. Therefore, using a cohort of ACT participants that is part of the UW ADRC Clinical Core (ACT-Plus), we will evaluate the specificity of DMN functional connectivity changes in preclinical AD, as well as MRI measures of the impact of cerebral microvascular disease. When successfully completed, this Project will have determined the utility of novel fMRI approaches to brain aging and preclinical AD in a sample that more closely reflects the ultimate target population.

Accepting Submissions for New Pilot Projects

Each year, in collaboration with the Friends of Alzheimer’s Research, we fund innovative Alzheimer’s-related projects by senior fellows and junior faculty. For the 2016–2017 research year, we are awarding pilot funding to projects that relate to our center’s theme: Precision Medicine for the Molecular and Clinical Complexity of Alzheimer’s Disease. Our long-term vision is to develop the knowledge and technology necessary for optimal targeting and timing of disease-modifying interventions that stop or slow Alzheimer’s disease.

Awards: Up to 3 one-year awards (5/1/16-4/30/17) of $30,000 direct costs each.

Eligibility: Applicants must be senior fellows or faculty of the UW at a rank no higher than assistant professor (acting titles accepted). Prior UW ADRC pilot awardees are ineligible.

Awards: Up to 3 one-year awards (5/1/16-4/30/17) of $30,000 direct costs each.

Application due by 4 PM on December 1, 2015, as a single pdf file to pricheso@uw.edu.

Application components:

  1. Cover letter addressing the following concerns:
    • How does this research relate to precision medicine for Alzheimers disease?
    • Why are existing resources inadequate for the proposed work?
    • How will the pilot project facilitate future independent funding?
    • List of three or more possible reviewers and any individuals to be excluded as reviewers
  2. Completed NIH form pages: Face page (Form Page 1), abstract (Form Page 2), budget page (Form Page 4), budget justifications (Form Page 5), biographical sketch(es) for key personnel, and Targeted/Planned Enrollment Table Format Page, if applicable. 
  3. Research plan (up to 4 pages of narrative, not including references): Follow the general NIH instructions for the Research Plan: http://grants1.nih.gov/grants/funding/phs398/phs398.html.
  4. Animal / human studies: If animals or humans are involved in your proposal, assurance of an IRB and/or IACUC application is required.
  5. Institutional approval: UW signatures are not required to submit. An eGC1 is not needed at the time of submission.

Award selection: Selection will be based upon (i) scientific merit, (ii) likelihood of leading to future funding, and (iii) alignment with the center theme of precision medicine for Alzheimer’s disease.

Notification of funding will occur prior to May 1, 2016.

Contact: Pema Richeson / 206.685.1221 / picheso@uw.edu.

Previously Funded Pilot Projects

Title: Health Education, Aerobic and Resistance Training (HEART) in Prediabetic African Americans
Project leader: Jeannine Skinner, PhD, UW Memory Wellness Center

Dr. Skinnner's project compared 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.

Title: Quantification of A-beta and Tau in CSF by LC-MS/MS
Project leader: Andrew Hoofnagle, MD, PhD

This project aimed to develop a new type of biomarker analysis to help translate already-known Alzheimer's biomarkers into practical, day-to-day diagnostic tests that could be reliably used in caring for people with Alzheimer's.

Title: Preclinical Study of D2 Antagonists for Neuroprotection Against Pathological Tau
Project leader: Brian Kraemer, PhD

Dr. Kraemer's project studied a compound (D2 antagonists) to see whether it was able to lessen tau development and toxicity through an animal model of Alzheimer's disease.

Title: Neuroimaging Biomakers of Cognitive Resilience Among APOE-4 Carriers
Project leader: Tara Madhyastha, PhD

The goal of this pilot study was to identify neuroimaging biomarkers associated with memory change in midlife that might represent a preclinical phase of Alzheimer's disease.