期刊
NEUROIMAGE-CLINICAL
卷 23, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2019.101828
关键词
Alzheimer's disease continuum; Gray matter structural covariance; AT(N) classification system; CSF; Tau protein; Amyloid
类别
资金
- National Key Research and Development Program of China [2016YFC1306600]
- Zhejiang Provincial Natural Science Foundation of China [LQ19H180006]
- Young Research Talents Fund, Chinese Medicine Science, and Technology Project of Zhejiang Province [2018ZQ035]
- Fundamental Research Funds for the Central Universities [2017XZZX001-01]
- Zhejiang Medicine and Health Science and Technology Program [2018KY418, 2016KYA099]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Eisai Inc.
- ElanPharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & D development t, LLC.
- J Johnson & Johnson PharmaceuticalResearch & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- MesoScaleDiagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis PharmaceuticalsCorporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
Alzheimer's disease (AD) has a long neuropathological accumulation phase before the onset of dementia. Such AD neuropathological deposition between neurons impairs the synaptic communication, resulting in networks disorganization. Our study aimed to explore the evolution patterns of gray matter structural covariance networks (SCNs) along AD continuum. Based on the AT(N) (i.e., Amyloid/Tau/Neurodegeneration) pathological classification system, we classified subjects into four groups using cerebrospinal fluid amyloid-beta(1-42) (A) and phosphorylated tau protein(181) (T). We identified 101 subjects with normal AD biomarkers (A-T-), 40 subjects with Alzheimer's pathologic change (A + T -), 101 subjects with biological AD (A + T +) and 91 AD with dementia (demented subjects with A + T +). We used four regions of interest to anchor default mode network (DMN, medial temporal subsystem and midline core subsystem), salience network (SN) and executive control network (ECN). Finally, we used a multi-regression model-based linear-interaction analysis to assess the SCN changes. Along the disease progression, DMN and SN showed increased structural association at the early stage while decreased structural association at the late stage. Moreover, ECN showed progressively increased structural association as AD neuropathological profiles progress. In conclusion, this study found the dynamic trajectory of SCNs changes along the AD continuum and support the network disconnection hypothesis underlying AD neuropathological progression. Further, SCN may potentially serve as an effective AD biomarker.
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