Investigating the association between cholinergic integrity and amyloid burden using cholinergic anatomy and [18F]‐FEOBV PET in individuals with Down Syndrome from the ABC‐DS and TRC‐DS cohorts

• Published in: Alzheimer's & dementia 2024-12, Vol.20 (S2), p.n/a
• Main Authors: Russell, Jason K, Conley, Alexander C, Boyd, Brian, Schlossberg, Rachel, Stranick, Allison, Rosenberg, Adam J, Acosta, Lealani Mae Y., Rafii, Michael, Shokouhi, Sepideh, Newhouse, Paul A
• Format: Article
• Language: English
• Subjects: Biomarkers
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.091823

Background Adults with Down Syndrome (DS) have the highest risk of developing Alzheimer’s disease (AD) worldwide. Triplication of the amyloid precursor protein gene on chromosome 21 results in early amyloid accumulation and Alzheimer’s pathology. The cholinergic system is known to decline early in the development of AD and plays a fundamental role in observed cognitive deficits. In the present work, we assess the association between amyloid accumulation and cholinergic integrity. Method 188 individuals from the ABC‐DS cohort (U01AG051406; U01AG051412; U19AG068054) were assessed cross‐sectionally. Basal forebrain volumes were calculated using the ScLimbic FreeSurfer pipeline for the basal forebrain (Ch1‐Ch4) and the DnSeg pipeline for Ch4 volumes. Linear regressions were performed between centiloid values, age, and basal forebrain volumes. Nine individuals recruited for a TRC‐DS sub‐study underwent a multimodal imaging assessment, including [11C]‐PiB PET and [18F]‐FEOBV PET imaging. Global centiloid values were calculated using PMOD, with regional SUVRs calculated using PetSurfer with GTM for partial volume corrections. Linear regressions were performed between global centiloid, regional [11C]‐PiB SUVR, and regional [18F]‐FEOBV SUVR. Result In ABC‐DS and the TRC‐DS sub‐study, global amyloid accumulation was positively associated with age (p