期刊
TRANSLATIONAL PSYCHIATRY
卷 11, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41398-021-01602-5
关键词
-
类别
资金
- National Natural Science Foundation of China [91849126, 81571245, 81771148]
- National Key R&D Program of China [2018YFC1314700]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute
- State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense award) [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.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- ADNI clinical sites in Canada
NIA-AA proposed a biological research framework to define Alzheimer's disease with dichotomized biomarker measurement, but it cannot characterize the hierarchical spreading pattern of tau pathology. A refined topographic F-18-AV-1451 tau PET staging scheme was constructed to reflect in vivo tau progression, showing potential in early diagnosis and disease mechanism study. Highly accumulated tau in temporal regions independently led to cognitive deterioration, indicating the importance of studying tau spreading pattern in Alzheimer's disease.
A biological research framework to define Alzheimer' disease with dichotomized biomarker measurement was proposed by National Institute on Aging-Alzheimer's Association (NIA-AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic F-18-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline F-18-AV-1451 tau PET (baseline age 73.9 +/- 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, using linear mixed-effect models and Cox proportional hazard models. Significant cognitive decline was first observed in stage 1 when tau levels only increased in transentorhinal regions. Rates of cognitive decline and clinical progression accelerated from stage 2 to stage 3 and stage 4. Higher stages were also associated with greater CSF phosphorylated tau and total tau concentrations from stage 1. Abnormal tau accumulation did not appear with normal beta-amyloid in neocortical regions but prompt cognitive decline by interacting with beta-amyloid in temporal regions. Highly accumulated tau in temporal regions independently led to cognitive deterioration. Topographic PET staging scheme have potentials in early diagnosis, predicting disease progression, and studying disease mechanism. Characteristic tau spreading pattern in Alzheimer's disease could be illustrated with biomarker measurement under NIA-AA framework. Clinical-neuroimaging-neuropathological studies in other cohorts are needed to validate these findings.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据