Ozsahin Ilker, Wang Xiuyuan, Zhou Liangdong, Xi Ke, Hojjati Seyed Hani, Tanzi Emily, Maloney Thomas, Fung Edward K, Dyke Jonathan P, Chen Kewei, Pahlajani Silky, McIntire Laura Beth, Costa Ana Paula, Dartora William Jones, Razlighi Qolamreza R, Glodzik Lidia, Li Yi, Chiang Gloria C, Rusinek Henry, de Leon Mony J, Butler Tracy A
Department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, 407 East 61st Street, 2nd floor, New York, NY, 10065, USA.
Operational Research Center in Healthcare, Near East University, Near East Boulevard, Nicosia/TRNC, 99138, Mersin 10, Turkey.
Sci Rep. 2025 Apr 14;15(1):12818. doi: 10.1038/s41598-025-97409-1.
Choroid plexus (CP), best known for producing CSF, also regulate inflammation and clear metabolic waste to maintain brain homeostasis. CP dysfunction is implicated in Alzheimer's Disease (AD), with MRI studies showing CP enlargement in AD. The basis for CP enlargement is unknown. We hypothesized that calcium deposition within CP, which increases with aging and in certain neurodegenerative conditions, might underlie pathologic CP enlargement and be linked to neurodegeneration. In 166 cognitively normal participants, we used multimodal imaging to examine CP structure (MRI-measured overall volume, CT-measured calcium volume), PET-measured Aβ, age, and APOE genotype as predictors of neurodegeneration, indexed as hippocampal volume. CP enlargement was associated with reduced hippocampal volume, particularly in APOE4 carriers. CP calcium was not independently associated with hippocampal volume. However, a significant interaction revealed APOE4 genotype-specific associations between CP calcium and neurodegeneration, with APOE4 carriers showing greater hippocampal volumes in association with greater CP calcium-opposite to our hypothesis. Results suggest that a factor other than calcium drives pathologic CP enlargement associated with neurodegeneration, with this factor especially important in APOE4 carriers. Candidate factors include lipids and inflammatory cells, which are known to accumulate in CP and be regulated by APOE. Our findings highlight CP as a critical locus for studying AD pathogenesis and the mechanisms by which APOE4 promotes AD.
脉络丛（CP）以产生脑脊液而闻名，它还能调节炎症并清除代谢废物以维持大脑内环境稳定。CP功能障碍与阿尔茨海默病（AD）有关，MRI研究显示AD患者的CP增大。CP增大的原因尚不清楚。我们推测，CP内的钙沉积可能是病理性CP增大的基础，并与神经退行性变有关，钙沉积会随着年龄增长和某些神经退行性疾病而增加。在166名认知正常的参与者中，我们使用多模态成像来检查CP结构（MRI测量的总体积、CT测量的钙体积）、PET测量的Aβ、年龄和APOE基因型，作为神经退行性变的预测指标，以海马体积作为索引。CP增大与海马体积减小有关，尤其是在APOE4携带者中。CP钙与海马体积无独立相关性。然而，一个显著的相互作用揭示了CP钙与神经退行性变之间的APOE4基因型特异性关联，APOE4携带者的海马体积与CP钙增加相关，这与我们的假设相反。结果表明，除钙以外的其他因素驱动了与神经退行性变相关的病理性CP增大，该因素在APOE4携带者中尤为重要。候选因素包括脂质和炎症细胞，已知它们会在CP中积累并受APOE调节。我们的研究结果突出了CP作为研究AD发病机制以及APOE4促进AD的机制的关键位点。
