Longitudinal investigation for enhancing Down Syndrome Research (LIFE‐DSR) Study: Tau PET and CSF sub‐studies. (1st February 2022)

• Record Type: Journal Article
• Authors: Hendrix, James A.; Britton, Angela; Christian, Bradley T.; Ledesma, Duvia Lara; Egan, Michael F.; Feldman, Howard; Hendrix, Suzanne B.; Herring, W. Joseph; Kennedy, Matthew E.; Nicodemus‐Johnson, Jessie; Revta, Carolyn; Struyk, Arie; Sur, Cyrille; Mobley, William C.
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.057426
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The Down syndrome (DS) population is aging rapidly with a life expectancy of nearly 60 years of age compared to 25 years of age in 1980. There are approximately 210, 000 people with DS in the USA and about 85, 000 are >30 years of age. 1 With longevity comes a high risk of Alzheimer's disease (AD). The lifetime risk of AD is estimated to be >90%, 2 and is the leading cause of death for adults with DS. 3 Symptoms of DS associated AD (DS‐AD) appear at approximately 45 to 55 years of age with early biomarker changes occurring a decade or more earlier at about 35 years of age. 4 Recent fluid biomarker and amyloid imaging data show that AD pathogenesis in individuals with DS are similar to AD biomarkers in individuals with late‐onset AD. 5 Published data using the tau positron emission tomography (PET) imaging agent flortaucipir provide data on tau accumulation in DS‐AD that correlates with amyloid burden 6 and cognitive decline 7 . Method: The LIFE‐DSR study is a multi‐center natural history study recruiting 270 adults with DS. Participants, age 25 or older, are followed at 16‐month intervals over 32‐months. Data collected includes cognitive, behavioral, and functional from a range of common developmental disability assessment tools. Plasma and buffy coat samples are banked for prospective molecular and genetic analyses. Result: Two longitudinal sub‐studies will be added to the LIFE‐DSR protocol. First is a tau PET sub‐study using the tracer 18 F‐MK‐6240. Second is a cerebrospinal fluid (CSF) biomarkers sub‐study. Both sub‐studies will enroll 30 LIFE‐DSR participants with similar demographics (age >= 35 years), collecting data twice every 16 months. Data from the tau PET and CSF sub‐studies will be compared with the clinical and fluid biomarker data collected under the LIFE‐DSR protocol. Conclusion: Inclusion of PET and CSF sub‐studies will enrich the LIFE‐DSR study and improve our ability to understand and assess clinical features, imaging, and genetic markers of DS‐AD progression and provide a basis for the development of endpoints for clinical trials to potentially develop more effective treatments. This is the first use of the next generation PET tau radiotracer, 18 F‐MK‐6240 in DS.