WRAP study receives $35 million renewal grant

The Wisconsin Registry for Alzheimer’s Prevention (WRAP) has been awarded a five-year, $35 million renewal grant from the National Institutes of Health, enabling continued in-depth study of biological indicators of Alzheimer’s disease that may signal the disease decades before the symptoms. The new funding will also enable expansion of the project to identify other causes of cognitive decline and enhance the diversity of the cohort through recruitment of people from communities historically under-represented in research.

WRAP is in the Wisconsin Alzheimer’s Institute at the University of Wisconsin Madison School of Medicine and Public Health. Founded in 2001, the study is the largest and one of the longest-running family history studies of Alzheimer’s disease in the world. WRAP includes more than 1,750 research volunteer participants, who return every other year for cognitive testing and optional brain imaging scans and lumbar puncture. These assessments provide researchers with a uniquely detailed look at how brain health changes over time in people with or without a parental family history of dementia.

“This research is progressing rapidly, and this funding will be critical to our future success,” said Sterling Johnson, PhD, principal investigator of WRAP. “Thanks to our dedicated research participants, WRAP is uniquely able to track biological signs of disease at the level of the individual, enabling a personalized medicine approach to examining why some people eventually develop symptoms of dementia and others do not.”

Next Steps: Focus on research diversity and exploring links to heart and brain health

The expanded funding will allow the study to offer expanded Alzheimer’s disease biomarkers to the entire cohort including positron emission tomography imaging of amyloid and tau (the two proteins that cause Alzheimer’s disease plaques and tangles), new blood-based biomarkers, and new vascular ultrasound examinations to research participants. Working with James Stein, MD, and the UW Atherosclerosis Imaging Research Program, data from these ultrasounds will investigate how vascular health of the vessels that supply the brain can influence and interact with future brain health. The additional funding will combine carotid ultrasounds to look more closely at the interplay between these factors and the participants’ brain health.

Gina Green Harris and Rebecca Koscik at WAI office

An essential focus of the study’s next five years will be continuing to increase inclusion of people from groups historically under-represented in research. WRAP is committed to increasing research participation of Latino and African American participants, from a current rate of 18 percent to more than 25 percent. The WRAP team will partner on recruitment efforts with the WAI Regional Milwaukee Office, led by Gina Green-Harris, MBA, that specializes in community engagement and provides culturally tailored programs and services. This new recruitment effort will also collaborate closely with an NIH-funded linked study to WRAP called African Americans Fighting Alzheimer’s in Midlife (AA-FAIM) led by Carey Gleason, PhD, MS.

“Increasing the diversity of our participants is one of our study’s primary goals,” Johnson said. “We will work with communities and individuals that have been under-represented in previous research to make sure our findings can be generalized to the people impacted by the disease.”

History of WRAP

The study started in 2001 and first received NIH funding in 2006. In 2008, the Wisconsin Alzheimer’s Institute opened the WAI regional Milwaukee Office, with a goal of improving access to care and resources and increasing African American research participation through culturally tailored programs and community engagement. Today, the WAI Regional Milwaukee Office includes a WRAP study satellite site. A second satellite site in La Crosse also hosts WRAP study visits.

A five-year, $19 million renewal grant in 2018 allowed WRAP to significantly increase its capacity to study biological indicators of Alzheimer’s disease, called biomarkers, that are identified in PET or MRI scans. WRAP expanded to offer brain imaging scans to participants. The study has completed more than 600 PET scans, 435 MRI scans, and 318 lumbar punctures; procedures established and conducted during the COVID-19 pandemic.

In 2021, an independent film crew released a documentary featuring WRAP participants and scientists. The documentary, Determined, aired in independent film festivals and appeared on PBS: NOVA in 2022 and is now available online or through streaming services.

WRAP data used worldwideWRAP study visit and PET scan

Each year, researchers from the UW-Madison campus and worldwide publish dozens of papers utilizing WRAP data, including these recent examples:

  • A publication in Nature Medicine in 2022 used WRAP data to study a newly identified blood marker called p-tau217. The scientists found that this simple blood test was a highly accurate and useful marker of disease progression even prior to symptoms, a finding that will be informative for studying the impact of new disease-modifying treatments.
  • Analyzing imaging data from WRAP, several UW–Madison researchers estimated a typical trajectory of amyloid duration is about 20.5 years at dementia onset; providing a greater understanding of an individual’s disease timeline that may increase diagnostic accuracy and opportunity for intervention and care.
  • Analyzing data from WRAP, UW–Madison colleagues published a study on the association of lifestyle health with cognition and amyloid accumulation; finding a healthier overall lifestyle is important for general cognition throughout mid-and-late life, but may not impact early Alzheimer’s disease-related protein accumulation or cognitive decline.

“For more than twenty years, we’ve formed a community of research participants and campus scientists partnering with researchers across the globe. Our role as a catalyst for discovery has become increasingly vital and powerful as the longitudinal data in the study accumulates,” Johnson said. “WRAP study participants are uniquely dedicated. They have a very high rate of return study visits – many participants have been enrolled in WRAP for more than a decade! In addition, many participants opt to undergo important procedures like PET scans or lumbar puncture that provide valuable biomarker data for us. It’s because of their determination and valuable contributions that we are now seeing significant strides in the science of Alzheimer’s disease prevention.”