Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load

被引：48

作者：

Calsolaro, Valeria ^{[1
]}

Matthews, Paul M. ^{[1
,2
]}

Donat, Cornelius K. ^{[1
,3
]}

Livingston, Nicholas R. ^{[1
]}

Femminella, Grazia D. ^{[1
]}

Guedes, Sandra Silva ^{[1
]}

Myers, Jim ^{[1
]}

Fan, Zhen ^{[1
]}

Tyacke, Robin J. ^{[1
]}

Venkataraman, Ashwin V. ^{[1
]}

Perneczky, Robert ^{[4
,5
,6
,7
]}

Gunn, Roger ^{[1
,8
]}

Rabiner, Eugenii A. ^{[8
,9
]}

Gentleman, Steve ^{[1
]}

Parker, Christine A. ^{[1
,10
]}

Murphy, Philip S. ^{[10
]}

Wren, Paul B. ^{[10
]}

Hinz, Rainer ^{[11
]}

Sastre, Magdalena ^{[1
]}

Nutt, David J. ^{[1
]}

Edison, Paul ^{[1
,12
]}

机构：

[1] Imperial Coll London, Dept Brain Sci, London, England

[2] Imperial Coll London, UK Dementia Res Inst, London, England

[3] Imperial Coll London, Ctr Blast Injury Studies, London, England

[4] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Psychiat & Psychotherapy, Munich, Germany

[5] German Ctr Neurodegenerat Disorders DZNE, Munich, Germany

[6] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[7] Imperial Coll London, Sch Publ Hlth, Ageing Epidemiol Res Unit AGE, London, England

[8] Invicro, London, England

[9] Kings Coll London, London, England

[10] GlaxoSmithKline, Stevenage, Herts, England

[11] Univ Manchester, Wolfson Mol Imaging Ctr, Manchester, Lancs, England

[12] Cardiff Univ, Cardiff, Wales

来源：

MOLECULAR PSYCHIATRY | 2021年 / 26卷 / 10期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

FIBRILLARY ACIDIC PROTEIN; ALZHEIMERS ASSOCIATION WORKGROUPS; POSITRON-EMISSION-TOMOGRAPHY; BINDING-SITES; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; PLAQUE DEPOSITION; DISEASE; BRAIN; EXPRESSION;

D O I：

10.1038/s41380-021-01193-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

C-11-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer's disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), F-18-florbetaben and C-11-BU99008 PET. The 8 amyloid (A beta)-positive CI subjects had higher C-11-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between C-11-BU99008 and F-18-florbetaben. Autoradiography using H-3-BU99008 with post-mortem Alzheimer's brains confirmed through visual assessment that increased H-3-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that C-11-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high A beta load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.

引用

页码：5848 / 5855

页数：8

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