Grazia Alice, Dyrba Martin, Pomara Nunzio, Temp Anna G, Grothe Michel J, Teipel Stefan J
Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald, Rostock, Germany.
J Prev Alzheimers Dis. 2025 Feb;12(2):100030. doi: 10.1016/j.tjpad.2024.100030. Epub 2025 Jan 1.
Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.
To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.
This is a cross-sectional study that analyzes baseline functional imaging data.
We obtained data from the Colombia cohort Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.
We analyzed data from 215 asymptomatic subjects carrying the presenilin-1 E280A mutation [64% female; 147 carriers (M = 35 years), 68 noncarriers (M = 40 years)].
We extracted functional magnetic resonance imaging data using seed-based connectivity analysis to examine the anterior and posterior subdivisions of the basal forebrain. Subsequently, we performed a Bayesian Analysis of Covariance to assess the impact of carrier status on functional connectivity in relation to amyloid positivity. For comparison, we also investigated hippocampus connectivity.
We found no effect of carrier status on anterior (Bayesian Factor = 1.167) and posterior basal forebrain connectivity (Bayesian Factor = 0.033). In carriers, we found no association of amyloid positivity with basal forebrain connectivity.
We falsified the hypothesis of basal forebrain connectivity reduction in preclinical mutation carriers with amyloid pathology. If replicated, these findings may not only confirm a discrepancy between familial and sporadic Alzheimer's disease, but also suggest new potential targets for future treatments.
影像学研究显示，前驱性散发性阿尔茨海默病患者胆碱能基底前脑早期萎缩，主观认知下降的淀粉样蛋白阳性个体基底前脑后部分功能连接减少。阿尔茨海默病家族性病例的类似研究仍很缺乏。
测试早老素-1 E280A突变携带者的基底前脑功能连接是否减少，以及这是否与淀粉样蛋白病理相关。
这是一项分析基线功能成像数据的横断面研究。
我们从哥伦比亚队列阿尔茨海默病预防计划常染色体显性阿尔茨海默病试验中获取数据。
我们分析了215名携带早老素-1 E280A突变的无症状受试者的数据[64%为女性；147名携带者（平均年龄35岁），68名非携带者（平均年龄40岁）]。
我们使用基于种子的连接分析提取功能磁共振成像数据，以检查基底前脑的前后分区。随后，我们进行了协方差贝叶斯分析，以评估携带者状态对与淀粉样蛋白阳性相关的功能连接的影响。为了进行比较，我们还研究了海马体连接。
我们发现携带者状态对基底前脑前区（贝叶斯因子=1.167）和后区连接（贝叶斯因子=0.033）没有影响。在携带者中，我们发现淀粉样蛋白阳性与基底前脑连接之间没有关联。
我们证伪了具有淀粉样蛋白病理的临床前突变携带者基底前脑连接减少的假设。如果得到重复验证，这些发现不仅可能证实家族性和散发性阿尔茨海默病之间的差异，还可能为未来治疗提出新的潜在靶点。
