路易体痴呆中的皮质微结构异常及其与阿尔茨海默病共病的关联。

Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer's disease copathologies.

作者信息

Mak Elijah, Reid Robert I, Przybelski Scott A, Fought Angela M, Lesnick Timothy G, Schwarz Christopher G, Senjem Matthew L, Raghavan Sheelakumari, Vemuri Prashanthi, Jack Clifford R, Min Hoon Ki, Jain Manoj K, Miyagawa Toji, Forsberg Leah K, Fields Julie A, Savica Rodolfo, Graff-Radford Jonathan, Jones David T, Botha Hugo, St Louis Erik K, Knopman David S, Ramanan Vijay K, Dickson Dennis W, Graff-Radford Neill R, Day Gregory S, Ferman Tanis J, Petersen Ronald C, Lowe Val J, Boeve Bradley F, O'Brien John T, Kantarci Kejal

机构信息

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

出版信息

NPJ Parkinsons Dis. 2025 May 12;11(1):124. doi: 10.1038/s41531-025-00944-x.

DOI:10.1038/s41531-025-00944-x

PMID:40355490

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12069582/

Abstract

Dementia with Lewy bodies (DLB) frequently coexists with Alzheimer's disease pathology, yet the pattern of cortical microstructural injury and its relationship with amyloid, tau, and cerebrovascular pathologies remains unclear. We applied neurite orientation dispersion and density imaging (NODDI) to assess cortical microstructural integrity in 57 individuals within the DLB spectrum and 57 age- and sex-matched cognitively unimpaired controls by quantifying mean diffusivity (MD), tissue-weighted neurite density index (tNDI), orientation dispersion index (ODI), and free water fraction (FWF). Amyloid and tau levels were measured using PiB and Flortaucipir PET imaging. Compared to controls, DLB exhibited increased MD and FWF, reduced tNDI across multiple regions, and focal ODI reductions in the occipital cortex. Structural equation modeling revealed that APOE genotype influenced amyloid levels, which elevated tau, leading to microstructural injury. These findings highlight the role of AD pathology in DLB neurodegeneration, advocating for multi-target therapeutic approaches addressing both AD and DLB-specific pathologies.

摘要

路易体痴呆（DLB）常与阿尔茨海默病病理共存，但皮质微结构损伤模式及其与淀粉样蛋白、tau蛋白和脑血管病理的关系仍不清楚。我们应用神经突方向离散度和密度成像（NODDI），通过量化平均扩散率（MD）、组织加权神经突密度指数（tNDI）、方向离散度指数（ODI）和自由水分数（FWF），评估57例DLB谱系个体及57例年龄和性别匹配的认知未受损对照的皮质微结构完整性。使用PiB和氟代tau蛋白PET成像测量淀粉样蛋白和tau蛋白水平。与对照组相比，DLB表现出MD和FWF增加、多个区域tNDI降低以及枕叶皮质局部ODI降低。结构方程模型显示，APOE基因型影响淀粉样蛋白水平，进而升高tau蛋白，导致微结构损伤。这些发现突出了AD病理在DLB神经退行性变中的作用，提倡针对AD和DLB特异性病理的多靶点治疗方法。