In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET

被引：197

作者：

Mecca, Adam P. ^{[1
,2
]}

Chen, Ming-Kai ^{[3
,5
]}

O'Dell, Ryan S. ^{[1
,2
]}

Naganawa, Mika ^{[3
]}

Toyonaga, Takuya ^{[3
]}

Godek, Tyler A. ^{[1
,2
]}

Harris, Joanna E. ^{[1
,2
]}

Bartlett, Hugh H. ^{[1
,2
]}

Zhao, Wenzhen ^{[1
,2
]}

Nabulsi, Nabeel B. ^{[3
]}

Vander Wyk, Brent C. ^{[4
]}

Varma, Pradeep ^{[3
]}

Arnsten, Amy F. T. ^{[5
]}

Huang, Yiyun ^{[3
]}

Carson, Richard E. ^{[3
]}

van Dyck, Christopher H. ^{[1
,2
,5
,6
]}

机构：

[1] Yale Univ, Sch Med, Alzheimers Dis Res Unit, One Church St,8th Floor, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA

[3] Yale Univ, Sch Med, Dept Radiol & Biomed Imaging, New Haven, CT USA

[4] Yale Univ, Sch Med, Program Aging, New Haven, CT USA

[5] Yale Univ, Sch Med, Dept Neurosci, New Haven, CT USA

[6] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA

来源：

ALZHEIMERS & DEMENTIA | 2020年 / 16卷 / 07期

基金：

美国国家卫生研究院;

关键词：

C-11]UCB-J vertical bar PET; Alzheimer's disease; SV2A; synaptic density; MILD COGNITIVE IMPAIRMENT; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; PREFRONTAL CORTEX; PROJECTIONS; PROGRESSION; MONKEY; RECOMMENDATIONS; QUANTIFICATION;

D O I：

10.1002/alz.12097

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density. Methods: We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [C-11]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio. Results: We observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume. Conclusion: We were able to measure widespread synaptic loss due to AD using [C-11]UCB-J PET. Future studies will continue to evaluate the utility of SV2A PET for tracking AD progression and for monitoring potential therapies.

引用

页码：974 / 982

页数：9

共 44 条

[1] The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease [J].