doi:10.3969/j.issn.2095-396.2016.03.004

Abstract

Abstract: Alzheimer’s disease （AD） is the main type of dementia，accounting for 50%~70% of dementia cases. With the emergence of population aging，the incidence and severity of AD are increasing，which brings great economic burden to families and society and attracts great attention from governments and scholars at home and abroad. Positron emission tomography （PET） can use different tracers for imaging to accurately monitor neuronal activity and brain tissue specific biochemical processes in vivo. Compared with other imaging techniques，PET has a high specificity and sensitivity to early diagnosis of AD. Therefore，it is very important for PET to develop more valuable PET tracers for AD. This paper summarizes the application of PET in the pathology diagnosis and curative effect for AD，and focuses on the role of PET in the early diagnosis and its progress.

Key words: positron emission tomography（PET）, Alzheimer&, rsquo, s disease（AD）, imaging technology, diagnosis

FENG Hui-li,WANG Peng-wen . [J]. Acta Neuropharmacologica, 2016, 6(3): 24-31.

References

[1]Alzheimer's Disease International. World Alzheimer Report 2015[J]. The Global Economic Impact of Dementia, 2015.

[2]Ph Scheltens, Kaj Blennow, Monique M B Breteler. Alzheimer's disease[J]. Lancet, 2016, 388 (10043): 505-517.

[3]Givoanni B Frisoni, Nick C Fox, Clifford R Jack, et al. The clinical use of structural MRI in Alzheimer disease[J].Nat Rev Neurol, 2010, 6(2): 67-77.

[4]John A Hardy, Gerald A Higgins. Alzheimer's disease: the amyloid cascade hypothesis[J]. Science, 1992, 256(5054): 184-185.

[5]Sanjay W Pimplikar, Ralph Nixon, Nixon K Robakis, et al. Amyloid-independent mechanisms in Alzheimer’s disease pathogenesis[J]. J Neurosci, 2010, 30(45): 14946-14954.

[6]Scheuner D E C, Christopher B Eckman, Malene Jensen, et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease[J]. Nat Med, 1996, 2(8): 864-870.

[7]Eric Karran, Marc Mercken, Bart De Strooper. The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics[J]. Nat Rev Drug Discov, 2011, 10(9): 698-712.

[8]Guy M McKhann, David S Knopman, Howard Chertkow, et al. The diagnosis of dementia due to Alzheimer's disease:recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease[J]. Alzheimers Dement, 2011, 7(3): 263-269.

[9]Lon S Schneider, Francesca Mangialasche, Niels Adreasen, et al. Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014[J]. J Intern Med, 2014, 275(3): 251-283.

[10]Jeffrey L Cummings, Travis Morstorf, Zhong Kate. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures[J]. Alzheimers Res Ther, 2014, 6(4): 37.

[11]Lon S Schneider, Mary Sano. Current Alzheimer’s disease clinical trials: methods and placebo outcomes[J]. Alzheimers Dement, 2009, 5(5): 388-397.

[12]Stephen Salloway, Reisa Sperling, Nick C Fox, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease[J]. N Engl J Med, 2014, 370(4): 322-333.

[13]Rachelle S Doody, Ronald G Thomas, Martin Farlow, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease[J]. N Engl J Med, 2014, 370(4): 311-321.

[14]Atri A, Colding-Jorgensen E. A 5HT-6 antagonist in advanced development for the treatment of mild-moderate Alzheimer’s disease[J]. J Prevent Alzheimer Dis, 2014, 3: 220.

[15]Rachelle S Doody, Rema Raman, Martin Farlow, et al. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease[J]. N Engl J Med, 2013, 369(4): 341-350.

[16]Andrew Lockhart. Imaging Alzheimer's disease pathology: one target, many ligands[J]. Drug Discov Today, 2006, 11(23-24): 1093-1099.

[17]Nobuyuki Okamura, Takahiro Suemoto, Hiroshi Shimadzu, et al. Styrylbenzoxazole derivatives for in vivo imaging of amyloid plaques in the brain[J]. J Neurosci, 2004, 24(10): 2535-2541.

[18]Jun Maeda, Ji Bin, Irie Toshiaki, et al. Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer’s disease enabled by positron emission tomography[J]. J Neurosci, 2007, 27(41): 10957-10968.

[19]Karl Herholz, Klaus Ebmeier. Clinical amyloid imaging in Alzheimer’s disease[J]. Lancet Neurol, 2011, 10(7): 667-670.

[20]Christopher M Clark, Michael J Pontecorvo, Thomas G Beach, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study[J].Lancet Neurol, 2012, 11(8) : 669-78.

[21]Natalie L Marchant, Bruce R Reed, Charles S DeCarli, et al. Cerebrovascular disease, beta-amyloid, and cognition in aging[J]. Neurobiol Aging, 2012, 33(5): 1006.

[22]Rik Ossenkoppele, Willemijn J Jansen, Gil D Rabinovici, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis[J].JAMA, 2015, 313(19): 1939-1949.

[23]Willemijn J Jansen, Rik Ossenkoppele, Dirk L Knol, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis[J]. JAMA, 2015, 313(19): 1924-1938.

[24]Marie Sarazin, Julien Lagarde, Michel Bottlaender. Distinct tau PET imaging patterns in typical and atypical Alzheimer’s disease[J]. Brain, 2016, 139(Pt 5): 1321-1324.

[25]Dietmar Thal, Rik Vandenberghe. Monitoring the progression of Alzheimer’s disease with tau-PET[J]. Brain, 2016, 139(Pt 5): 1318-1320.

[26]Victor L Villemagne, Michelle T Fodero-Tavoletti, Colin L Masters, et al. Tau imaging: early progress and future directions[J]. Lancet Neurol, 2015, 14(1): 114-124.

[27]Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, et al. [18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer’s disease[J]. Eur J Nucl Med Mol Imaging, 2015, 42(7): 1052-1061.

[28]Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, et al. 18F-THK5351: a novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer disease[J]. J Nucl Med, 2016, 57(2): 208-214.

[29]Dustin W Wooten, Nicolas Guehl, Eline E Verwer, et al. Pharmacokinetic evaluation of the tau PET radiotracer [18F]T807 ([18F]AV-1451) in human subjects[J]. J Nucl Med, 2017, 58(3): 484-491.

[30]Marta Marquie, Marc D Normandin, Avery C Meltzer, et al. Pathological correlations of [F-18]-AV-1451 imaging in non-Alzheimer tauopathies[J]. Ann Neurol, 2017, 81(1): 117-128.

[31]Masahiro Maruyama, Hitoshi Shimada, Tetsuya Suhara, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls[J]. Neuron, 2013, 79(6): 1094-1108.

[32]Rik Ossenkoppele, Daniel R Schonhaut, Suzanne Baker, et al. Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy[J]. Ann Neurol, 2015, 77(2): 338-342.

[33] John C Morris. Dementia update 2005[J]. Alzheimer Dis Assoc Disord, 2005, 19 (2):100-117.

[34]M J de Leon, Ajax George, Steven H Ferris, et al. Regional correlation of PET and CT in senile dementia of the Alzheimer type[J]. AJNR Am J Neuroradiol, 1983, 4(3): 553-556.

[35] Richard Wurtman. Biomarkers in the diagnosis and management of Alzheimer’s disease[J]. Metabolism, 2015, 64(3 Suppl 1): S47-50.

[36] Samuel T Henderson. High carbohydrate diets and Alzheimer's disease[J]. Med Hypotheses, 2004, 62(5): 689-700.

[37] Eric M Reiman, Chen Ke-wei, Gene E Alexander, et al. Functional brain abnormalities in young adults at genetic risk for late-onsetczheimer's dementia[J]. Proc Natl Acad Sci U S A, 2004, 101 (1): 284-289.

[38] Daniela Perani, Pasquale Anthony Della Rosa, Chiara Cerami, et al. Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting[J]. Neuroimage Clin, 2014, 6: 445- 454.

[39]Kyle B Womack, Ramon Diaz-Arrastia, Howard J Aizenstein, et al. Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors[J]. Arch Neurol, 2011, 68(3): 329-337.

[40] Jagust W J, Seab J P, Huesman R H, et al. Diminished glucose transport in Alzheimer’s disease: Dynamic pet studies[J]. J Cereb Blood Flow Metab, 1991, 11(2): 323-330.

[41] Piert M, Koeppe RA, Giordani B, et al. Diminished glucose transport and phosphorylation in Alzheimer’s disease determined by dynamic FDG-PET[J]. J Nucl Med,1996,37 (2):201-208.

[42]冯慧利, 高凯, 魏鹏, 等. MicroPET观察姜黄素对9月龄AD小鼠脑葡萄糖代谢的影响[J]. 中国实验动物学报, 2013, 21(4): 38-41.

[43]Rachel M Nicholson, Yael Kusne, Lee A Nowak, et al. Regional cerebral glucose uptake in the 3×tg model of alzheimer’s disease highlights common regional vulnerability across ad mouse models[J]. Brain Res, 2010, 1347: 179-185.

[44] Roman Roy, Flavia Niccolini, Gennaro Pagano, et al. Cholinergic imaging in dementia spectrum disorders[J]. Eur J Nucl Med Mol Imaging, 2016, 43(7): 1376-1386.

[45] Kuhl D E, Koeppe R A, Minoshima S, et al. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease[J]. Neurology, 1999, 52(4): 691-699.

[46] Herholz K, Weisenbach S, Zu¨ndorf G, et al. In vivo study of acetylcholine esterase in basal forebrain,amygdala, and cortex in mild to moderate Alzheimer disease[J]. Neuroimage, 2004, 21(1): 136-143.

[47] Henry N Wagner. Nuclear medicine for all the world--from molecular imaging to molecular medicine[J]. J Korean Med Sci, 2007, 22(4): 595-597.

[48] Susanne G Mueller, Michael W Weiner, Leon J Thal, et al. Ways toward an early diagnosis in Alzheimer's disease: the Alzheimer's Disease Neuroimaging Initiative (ADNI)[J]. Alzheimers Dement, 2005, 1(1): 55-66.

[49] Herholz K, Salmon E, Perani D, et al. Discrimination between Alzhei-mer dementia and controls by automated analysis of multicenter FDG PET[J]. Neuroimage, 2002, 17(1): 302-316.

[50] Chételat G, Desgranges B, de la Sayette V, et al. Mild cognitive impairment: Can FDG-PET predict who is to rapidly convert to Alzheimer's disease[J]? Neurology, 2003, 60(8): 1374-1377.

[51]Gary W Small, Susan Y Bookheimer, Paul M Thompson, et al. Current and future uses of neuroimaging for cognitively impaired patients[J].Lancet Neurol, 2008, 7(2): 161-172.

[52]李德鹏, 马云川, 苏玉盛, 等. 老年性痴呆与血管性痴呆的18F-FDG PET显像分析[J]. 中风与神经疾病杂志, 2001, 18(4): 213-214.

[53]Nacer Kerrouche, Karl Herholz, Renee Mielke, et al. 18FDG PET in vascular dementia: differentiation from Alzheimer's disease using voxel-based multivariate analysis[J]. J Cereb Blood Flow Metab, 2006, 26(9): 1213-1221.

[54]Yuan Y, Gu Z X, Wei W S. Fluorodeoxyglucosepositron-emission tomography, single-photon emission tomography, and structural MR imaging for prediction of rapid conversion to Alzheimer disease in patients with mild cognitive impairment:a meta-analysis[J]. AJNR Am J Neuroradiol, 2009, 30(2): 404-410.

[55]Zhang S, Han D, Tan X, et al. Diagnostic accuracy of 18F-FDG and 11C-PIB-PET for prediction of shortterm conversion to Alzheimer’s disease in subjects with mild cognitive impairment[J]. Int J Clin Pract, 2012, 66(2):185-198.

[56]Jennifer L Shaffer, Jeffrey R Petrella, Forrest C Sheldon, et al. Predicting cognitive decline in subjects at risk for Alzheimer disease by using combined cerebrospinal fluid, MR imaging, and PET biomarkers[J]. Radiology, 2013, 266(2): 583-591.

[57]Daniel H S Silverman, Gary W Small, Carol Y Chang, et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome[J]. JAMA, 2001, 286(17): 2120-2127.

[58]王世真, 朴日阳, 张春. 分子核医学(第二版) [M]. 中国协和医科大学出版社, 2004: 392-396.

[59]Kuhl D E, Minoshima S, Frey K A, et al. Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex[J]. Ann Neurol, 2000, 48(3): 391-395.

[60]Bohnen N I, Kaufer D I, Hendrickson R, et al. Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer’s disease[J]. J Neurol Neurosurg Psychiatry, 2005, 76(3): 315-319.

[61]Kadir A, Darreh-Shori T, Almkvist O, et al. PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD[J]. Neurobiol Aging, 2008, 29(8): 1204-1217.

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