Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Gehlsheimer Str. 20, 18147, Rostock, Germany.
Department of Psychosomatic Medicine, University Medicine Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany.
Sci Rep. 2024 May 17;14(1):11268. doi: 10.1038/s41598-024-60799-9.
We aimed to study atrophy and glucose metabolism of the cholinergic basal forebrain in non-demented mutation carriers for autosomal dominant Alzheimer's disease (ADAD). We determined the level of evidence for or against atrophy and impaired metabolism of the basal forebrain in 167 non-demented carriers of the Colombian PSEN1 E280A mutation and 75 age- and sex-matched non-mutation carriers of the same kindred using a Bayesian analysis framework. We analyzed baseline MRI, amyloid PET, and FDG-PET scans of the Alzheimer's Prevention Initiative ADAD Colombia Trial. We found moderate evidence against an association of carrier status with basal forebrain volume (Bayes factor (BF) = 0.182). We found moderate evidence against a difference of basal forebrain metabolism (BF = 0.167). There was only inconclusive evidence for an association between basal forebrain volume and delayed memory and attention (BF = 0.884 and 0.184, respectively), and between basal forebrain volume and global amyloid load (BF = 2.1). Our results distinguish PSEN1 E280A mutation carriers from sporadic AD cases in which cholinergic involvement of the basal forebrain is already detectable in the preclinical and prodromal stages. This indicates an important difference between ADAD and sporadic AD in terms of pathogenesis and potential treatment targets.
我们旨在研究非痴呆性常染色体显性阿尔茨海默病（ADAD）突变携带者的胆碱能基底前脑的萎缩和葡萄糖代谢。我们使用贝叶斯分析框架，确定了 167 名哥伦比亚 PSEN1 E280A 突变非痴呆携带者和 75 名同一家族年龄和性别匹配的非突变携带者的基底前脑萎缩和代谢受损的证据水平。我们分析了阿尔茨海默病预防倡议 ADAD 哥伦比亚试验的基线 MRI、淀粉样蛋白 PET 和 FDG-PET 扫描。我们发现，携带状态与基底前脑体积之间存在中度关联（贝叶斯因子 (BF) = 0.182）的证据不足。我们发现，携带状态与基底前脑代谢之间存在中度关联（BF = 0.167）的证据不足。基底前脑体积与延迟记忆和注意力之间存在关联的证据仅不明确（BF 分别为 0.884 和 0.184），基底前脑体积与总淀粉样蛋白负荷之间存在关联的证据也不明确（BF 分别为 2.1）。我们的研究结果将 PSEN1 E280A 突变携带者与散发性 AD 病例区分开来，在散发性 AD 病例中，基底前脑的胆碱能参与在临床前和前驱期已经可以检测到。这表明 ADAD 和散发性 AD 在发病机制和潜在治疗靶点方面存在重要差异。
