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

共 60 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].

Albert, Marilyn S. ;

DeKosky, Steven T. ;

Dickson, Dennis ;

Dubois, Bruno ;

Feldman, Howard H. ;

Fox, Nick C. ;

Gamst, Anthony ;

Holtzman, David M. ;

Jagust, William J. ;

Petersen, Ronald C. ;

Snyder, Peter J. ;

Carrillo, Maria C. ;

Thies, Bill ;

Phelps, Creighton H. .

ALZHEIMERS & DEMENTIA, 2011, 7 (03) :270-279

[2] Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation [J].

Belanger, Mireille ;

Allaman, Igor ;

Magistretti, Pierre J. .

CELL METABOLISM, 2011, 14 (06) :724-738

[3] Neuroanatomy and Pathology of Sporadic Alzheimer's Disease Prologue [J].

Braak, Heiko ;

Del Tredici, Kelly .

NEUROANATOMY AND PATHOLOGY OF SPORADIC ALZHEIMER'S DISEASE, 2015, 215 :1-2

[4] Optimized classification of 18F-Florbetaben PET scans as positive and negative using an SUVR quantitative approach and comparison to visual assessment [J].

Bullich, Santiago ;

Seibyl, John ;

Catafau, Ana M. ;

Jovalekic, Aleksandar ;

Koglin, Norman ;

Barthel, Henryk ;

Sabri, Osama ;

De Santi, Susan .

NEUROIMAGE-CLINICAL, 2017, 15 :325-332

[5] Astrocyte and Alzheimer's disease [J].

Cai, Zhiyou ;

Wan, Cheng-Qun ;

Liu, Zhou .

JOURNAL OF NEUROLOGY, 2017, 264 (10) :2068-2074

[6] Neuroinflammation in Alzheimer's disease: Current evidence and future directions [J].

Calsolaro, Valeria ;

Edison, Paul .

ALZHEIMERS & DEMENTIA, 2016, 12 (06) :719-732

[7] Astrocyte Biomarkers in Alzheimer's Disease [J].

Carter, Stephen F. ;

Herholz, Karl ;

Rosa-Neto, Pedro ;

Pellerin, Luc ;

Nordberg, Agneta ;

Zimmer, Eduardo R. .

TRENDS IN MOLECULAR MEDICINE, 2019, 25 (02) :77-95

[8] Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG [J].

Carter, Stephen F. ;

Scholl, Michael ;

Almkvist, Ove ;

Wall, Anders ;

Engler, Henry ;

Langstrom, Bengt ;

Nordberg, Agneta .

JOURNAL OF NUCLEAR MEDICINE, 2012, 53 (01) :37-46

[9] Biological parametric mapping: A statistical toolbox for multimodality brain image analysis [J].

Casanova, Ramon ;

Srikanth, Ryali ;

Baer, Aaron ;

Laurienti, Paul J. ;

Burdett, Jonathan H. ;

Hayasaka, Satoru ;

Flowers, Lynn ;

Wood, Frank ;

Maldjian, Joseph A. .

NEUROIMAGE, 2007, 34 (01) :137-143

[10] IFN-γ Promotes Complement Expression and Attenuates Amyloid Plaque Deposition in Amyloid β Precursor Protein Transgenic Mice [J].

Chakrabarty, Paramita ;

Ceballos-Diaz, Carolina ;

Beccard, Amanda ;

Janus, Christopher ;

Dickson, Dennis ;

Golde, Todd E. ;

Das, Pritam .

JOURNAL OF IMMUNOLOGY, 2010, 184 (09) :5333-5343

← 1 2 3 4 5 6 →