Earlier Alzheimer's disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading.
Earlier Alzheimer's disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading.
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DOI：
10.1038/s41467-022-32592-7
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发表时间：
2022-08-20
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
在阿尔茨海默病（AD）中，较年轻的症状发作与加速的疾病进展和tau扩散相关，但更快的疾病表现的潜在机制尚不清楚。为了解决这一问题，我们在对照组和生物标记物证实的AD患者（ADNI/BioFINDER，n = 240/57）的两个独立样本中结合了静息态fMRI和纵向tau-PET。在两个样本中一致，我们发现年轻的症状性AD患者在全球连接的额顶叶枢纽中显示出更强的tau-PET，即，这些区域对于维持AD的认知至关重要。枢纽中更强的tau-PET预测了随后更快的tau积累，这表明全球相连区域中的tau促进了连接性介导的tau传播。此外，枢纽中更强的tau-PET介导了症状性AD患者中年龄更小和tau积累更快之间的关联，这预示着认知能力下降更快。这些独立验证的研究结果表明，年轻的AD症状发作与大脑中枢中更强的tau病理学有关，并加速了tau在整个连接的大脑区域和认知能力下降中的扩散。年轻发病的散发性阿尔茨海默病患者表现出更快的病理和临床进展。在这里，作者报告说，阿尔茨海默病的早期症状发作与全球连接的大脑枢纽中较高的tau病理学，加速连接介导的tau传播和更快的认知衰退有关。
In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline. Individuals with young onset sporadic Alzheimer’s disease show faster pathological and clinical progression. Here the authors report that earlier symptom onset in Alzheimer’s disease is associated with higher tau pathology in globally connected brain hubs, accelerated connectivity-mediated tau spreading and faster cognitive decline.
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DOI：
10.1186/s13195-021-00880-x
发表时间：
2021-08-12
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Biel D;Brendel M;Rubinski A;Buerger K;Janowitz D;Dichgans M;Franzmeier N;Alzheimer’s Disease Neuroimaging Initiative (ADNI)
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
影响因子：
3.2
作者：
Crane, Paul K.;Carle, Adam;Gibbons, Laura E.;Insel, Philip;Mackin, R. Scott;Gross, Alden;Jones, Richard N.;Mukherjee, Shubhabrata;Curtis, S. McKay;Harvey, Danielle;Weiner, Michael;Mungas, Dan
通讯作者：
Mungas, Dan
DOI：
10.3233/jad-170360
发表时间：
2017
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Franzmeier N;Hartmann JC;Taylor ANW;Araque Caballero MÁ;Simon-Vermot L;Buerger K;Kambeitz-Ilankovic LM;Ertl-Wagner B;Mueller C;Catak C;Janowitz D;Stahl R;Dichgans M;Duering M;Ewers M
通讯作者：
Ewers M
影响因子：
7.7
作者：
Adams, Jenna N.;Maass, Anne;Jagust, William J.
通讯作者：
Jagust, William J.
影响因子：
14.5
作者：
Ewers, Michael;Luan, Ying;Franzmeier, Nicolai
通讯作者：
Franzmeier, Nicolai