Russell Jason K, Conley Alexander C, Boyd Brian D, Begnoche J Patrick, Schlossberg Rachel, Stranick Allison, Rosenberg Adam J, Acosta Lealani Mae Y, Martin Dann, Neal Yasmeen, Kanel Prabesh, Albin Roger L, Rafii Michael S, Dumas Julie, Newhouse Paul A
Center for Cognitive Medicine, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
medRxiv. 2024 Nov 1:2024.10.28.24316136. doi: 10.1101/2024.10.28.24316136.
Adults with Down syndrome are genetically predisposed to developing Alzheimer's disease after the age of 40. The cholinergic system, which is critical for cognitive functioning, is known to decline in Alzheimer's disease and although first investigated in individuals with Down syndrome 40 years ago, remains relatively understudied. Existing studies suggest individuals with Down syndrome have an intact cholinergic system at birth that declines through adulthood alongside the development of Alzheimer's disease pathology. The present study provides the first description of cholinergic terminals in vivo in non-demented adults with Down syndrome utilizing [F]-fluoroethoxybenzovesamicol PET imaging. In addition, we investigated age-associated decline in cholinergic terminal density. Sixteen non-demented adults with Down syndrome and 20 neurotypically developed individuals were studied, comparing radiotracer uptake groupwise and associations with age utilizing a voxel-based approach. Adults with Down syndrome displayed significantly increased [F]-fluoroethoxybenzovesamicol uptake in the cerebellum, brainstem, thalamus, and numerous cortical regions compared to age-matched controls. Cholinergic terminal density in numerous cortical regions showed a steeper decline associated with increasing age in adults with Down syndrome than observed in neurotypically developed adults in the age range tested. These data suggest increased cholinergic terminal density in early adulthood in individuals with Down syndrome with a more rapid or earlier age-associated decline than is observed in neurotypically developed individuals.
患有唐氏综合征的成年人在40岁后有患阿尔茨海默病的遗传倾向。胆碱能系统对认知功能至关重要，在阿尔茨海默病中已知会衰退，尽管40年前就开始在唐氏综合征患者中进行研究，但仍相对研究不足。现有研究表明，唐氏综合征患者出生时胆碱能系统完好，随着成年期阿尔茨海默病病理的发展而衰退。本研究首次利用[F] - 氟乙氧基苯甲戊铵PET成像描述了非痴呆唐氏综合征成年患者体内的胆碱能终末。此外，我们研究了胆碱能终末密度与年龄相关的下降情况。研究了16名非痴呆唐氏综合征成年人和20名发育正常个体，采用基于体素的方法按组比较放射性示踪剂摄取情况以及与年龄的关联。与年龄匹配的对照组相比，唐氏综合征成年人在小脑、脑干、丘脑和许多皮质区域的[F] - 氟乙氧基苯甲戊铵摄取显著增加。在测试年龄范围内，唐氏综合征成年人许多皮质区域的胆碱能终末密度随年龄增长的下降比发育正常的成年人更陡峭。这些数据表明，唐氏综合征个体在成年早期胆碱能终末密度增加，且与年龄相关的下降比发育正常个体更快或更早。
