Imaging of glutamate neurotransmitter alterations in Alzheimer's disease

被引:115
作者
Haris, Mohammad [1 ]
Nath, Kavindra [2 ]
Cai, Kejia [1 ]
Singh, Anup [1 ]
Crescenzi, Rachelle [1 ]
Kogan, Feliks [1 ]
Verma, Gaurav [2 ]
Reddy, Sanjana [1 ]
Hariharan, Hari [1 ]
Melhem, Elias R. [2 ]
Reddy, Ravinder [1 ]
机构
[1] Univ Penn, Dept Radiol, Ctr Magnet Resonance & Opt Imaging, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
Alzheimer's disease; brain; glutamate; MRS; MRI; chemical exchange saturation transfer imaging; IN-VIVO; COGNITIVE IMPAIRMENT; EARLY-DIAGNOSIS; SPECTROSCOPY;
D O I
10.1002/nbm.2875
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Glutamate (Glu) is a major excitatory neurotransmitter in the brain and has been shown to decrease in the early stages of Alzheimer's disease (AD). Using a glutamate chemical (amine) exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in the APP-PS1 transgenic mouse model of AD at high spatial resolution. Compared with wild-type controls, AD mice exhibited a notable reduction in GluCEST contrast (similar to 30%) in all areas of the brain. The change in [Glu] was further validated through 1H MRS. A positive correlation was observed between GluCEST contrast and 1H MRS-measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for the diagnosis of the disease in preclinical stages and enables the development of disease-modifying therapies for AD. Copyright (c) 2012 John Wiley & Sons, Ltd.
引用
收藏
页码:386 / 391
页数:6
相关论文
共 30 条
[1]  
Ametamey SM, 2007, J NUCL MED, V48, P247
[2]   Decreased glutamate plus glutamine in Alzheimer's disease detected in vivo with 1H-MRS at 0.5 T [J].
Antuono, PG ;
Jones, JL ;
Wang, Y ;
Li, SJ .
NEUROLOGY, 2001, 56 (06) :737-742
[3]   Forecasting the global burden of Alzheimer's disease [J].
Brookmeyer, Ron ;
Johnson, Elizabeth ;
Ziegler-Graham, Kathryn ;
Arrighi, H. Michael .
ALZHEIMERS & DEMENTIA, 2007, 3 (03) :186-191
[4]   Magnetic resonance imaging of glutamate [J].
Cai, Kejia ;
Haris, Mohammad ;
Singh, Anup ;
Kogan, Feliks ;
Greenberg, Joel H. ;
Hariharan, Hari ;
Detre, John A. ;
Reddy, Ravinder .
NATURE MEDICINE, 2012, 18 (02) :302-306
[5]   Role of Myo-Inositol by Magnetic Resonance Spectroscopy in Early Diagnosis of Alzheimer's Disease in APP/PS1 Transgenic Mice [J].
Chen, Shuang-Qing ;
Wang, Pei-Jun ;
Ten, Gao-Jun ;
Zhan, Wei ;
Li, Ming-Hua ;
Zang, Feng-Chao .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2009, 28 (06) :558-566
[6]   Looking backward to move forward: Early detection of neurodegenerative disorders [J].
Dekosky, ST ;
Marek, K .
SCIENCE, 2003, 302 (5646) :830-834
[7]   Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance [J].
Ewers, Michael ;
Walsh, Cathal ;
Trojanowski, John Q. ;
Shaw, Leslie M. ;
Petersen, Ronald C. ;
Jack, Clifford R., Jr. ;
Feldman, Howard H. ;
Bokde, Arun L. W. ;
Alexander, Gene E. ;
Scheltens, Philip ;
Vellas, Bruno ;
Dubois, Bruno ;
Weiner, Michael ;
Hampel, Harald .
NEUROBIOLOGY OF AGING, 2012, 33 (07) :1203-+
[8]   CORTICAL PYRAMIDAL NEURON LOSS MAY CAUSE GLUTAMATERGIC HYPOACTIVITY AND COGNITIVE IMPAIRMENT IN ALZHEIMERS-DISEASE - INVESTIGATIVE AND THERAPEUTIC PERSPECTIVES [J].
FRANCIS, PT ;
SIMS, NR ;
PROCTER, AW ;
BOWEN, DM .
JOURNAL OF NEUROCHEMISTRY, 1993, 60 (05) :1589-1604
[9]   Glutamatergic systems in Alzheimer's disease [J].
Francis, PT .
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, 2003, 18 :S15-S21
[10]   Biomarkers for Alzheimer's disease therapeutic trials [J].
Hampel, Harald ;
Wilcock, Gordon ;
Andrieu, Sandrine ;
Aisen, Paul ;
Blennow, Kaj ;
Broich, K. ;
Carrillo, Maria ;
Fox, Nick C. ;
Frisoni, Giovanni B. ;
Isaac, Maria ;
Lovestone, Simon ;
Nordberg, Agneta ;
Prvulovic, David ;
Sampaio, Christina ;
Scheltens, Philip ;
Weiner, Michael ;
Winblad, Bengt ;
Coley, Nicola ;
Vellas, Bruno .
PROGRESS IN NEUROBIOLOGY, 2011, 95 (04) :579-593