دورية أكاديمية
Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease.
| العنوان: | Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease. |
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| المؤلفون: | Wang J; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China., Huang Q; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China., Chen X; Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 310000, China., You Z; Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 310000, China., He K; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China., Guo Q; Department of Gerontology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, 200233, China., Huang Y; PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, CT, 06520-8048, USA., Yang Y; Beijing United Imaging Research Institute of Intelligent Imaging, Beijing, 100089, China., Lin Z; Central Research Institute, United Imaging Healthcare Group Co., Ltd, Shanghai, 201807, China., Guo T; Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, 518000, China., Zhao J; Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 310000, China., Guan Y; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China. guanyihui@hotmail.com., Li B; Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. libinyin@126.com., Xie F; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China. Fangxie@fudan.edu.cn. |
| المصدر: | Molecular psychiatry [Mol Psychiatry] 2024 Sep; Vol. 29 (9), pp. 2799-2809. Date of Electronic Publication: 2024 Apr 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996- |
| مواضيع طبية MeSH: | Alzheimer Disease*/metabolism , Alzheimer Disease*/pathology , Alzheimer Disease*/diagnostic imaging , tau Proteins*/metabolism , Amyloid beta-Peptides*/metabolism , Synapses*/metabolism , Synapses*/pathology , Cognitive Dysfunction*/metabolism , Positron-Emission Tomography*/methods, Humans ; Female ; Male ; Aged ; Middle Aged ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology ; Brain/metabolism ; Brain/pathology ; Brain/diagnostic imaging ; Aged, 80 and over ; Positron Emission Tomography Computed Tomography/methods ; Magnetic Resonance Imaging/methods |
| مستخلص: | The associations of synaptic loss with amyloid-β (Aβ) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [ 18 F]SynVesT-1 PET/MR scans to assess synaptic density and [ 18 F]florbetapir and [ 18 F]MK6240 PET/CT scans to evaluate Aβ plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aβ42/40 and p-tau181 levels measured by the Simoa platform. Twenty-three individuals, 6 AD patients, 4 MCI patients, and 13 NCs, underwent [ 18 F]SynVesT-1 PET/MRI and [ 18 F]MK6240 PET/CT scans during a one-year follow-up assessment. The associations of Aβ and tau pathology with cross-sectional and longitudinal synaptic loss were investigated using Pearson correlation analyses, generalized linear models and mediation analyses. AD patients exhibited lower synaptic density than NCs and MCI patients. In the whole cohort, global Aβ deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes. Synaptic density in almost all regions was related to the corresponding regional tau tangles independent of global Aβ deposition in the whole cohort and stratified groups. Synaptic density in the medial and lateral temporal lobes was correlated with plasma Aβ42/40 (r = 0.300, p = 0.020/r = 0.289, p = 0.025) and plasma p-tau 181 (r = -0.412, p = 0.001/r = -0.529, p < 0.001) levels in the whole cohort. Mediation analyses revealed that tau tangles mediated the relationship between Aβ plaques and synaptic density in the whole cohort. Baseline tau pathology was positively associated with longitudinal synaptic loss. This study suggested that tau burden is strongly linked to synaptic density independent of Aβ plaques, and also can predict longitudinal synaptic loss. (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.) |
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| المشرفين على المادة: | 0 (tau Proteins) 0 (Amyloid beta-Peptides) 0 (MAPT protein, human) |
| تواريخ الأحداث: | Date Created: 20240408 Date Completed: 20240924 Latest Revision: 20240924 |
| رمز التحديث: | 20240925 |
| DOI: | 10.1038/s41380-024-02501-z |
| PMID: | 38589563 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-5578 |
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| DOI: | 10.1038/s41380-024-02501-z |