Biomarkers for Alzheimer's disease-preparing for a new era of disease-modifying therapies

被引:251
作者
Zetterberg, Henrik [1 ,2 ,3 ,4 ]
Bendlin, Barbara B. [5 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
[2] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
[3] UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England
[4] UCL, UK Dementia Res Inst, London, England
[5] Univ Wisconsin Madison, Univ Wisconsin Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53706 USA
基金
欧洲研究理事会; 瑞典研究理事会; 英国医学研究理事会;
关键词
CEREBROSPINAL-FLUID LEVELS; AMYLOID-BETA; SYNAPTIC PROTEIN; BRAIN; TAU; PLASMA; NEUROGRANIN; DIAGNOSIS; CSF; ATROPHY;
D O I
10.1038/s41380-020-0721-9
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
Clinical trial results presented in 2019 suggest that antibody-based removal of cerebral amyloid beta (A beta) plaques may possibly clear tau tangles and modestly slow cognitive decline in symptomatic Alzheimer's disease (AD). Although regulatory approval of this approach is still pending, preparing the healthcare system for the advent of disease-modifying therapies against AD is imperative. In particular, it will be necessary to identify the most suitable biomarkers to facilitate appropriate treatment of AD. Here, we give an update on recent developments in fluid and imaging biomarkers for AD-related pathologies and discuss potential approaches that could be adopted to screen for and clarify the underlying pathology in people seeking medical advice because of cognitive symptoms. We succinctly review recent data regarding biomarkers for A beta and tau pathology, neurodegeneration, synaptic dysfunction, and inflammation, highlight the need for further research into common copathologies, and suggest how different biomarkers could be used (most likely in combination) to facilitate the development and clinical implementation of novel drug candidates against AD.
引用
收藏
页码:296 / 308
页数:13
相关论文
共 109 条
[1]   Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer's disease treatment studies [J].
Alexander, GE ;
Chen, K ;
Pietrini, P ;
Rapoport, SI ;
Reiman, EM .
AMERICAN JOURNAL OF PSYCHIATRY, 2002, 159 (05) :738-745
[2]   Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: A View of the Regulatory Science Qualification Landscape from the Coalition Against Major Diseases CSF Biomarker Team [J].
Arneric, Stephen P. ;
Batrla-Utermann, Richard ;
Beckett, Laurel ;
Bittner, Tobias ;
Blennow, Kaj ;
Carter, Leslie ;
Dean, Robert ;
Engelborghs, Sebastiaan ;
Genius, Just ;
Gordon, Mark Forrest ;
Hitchcock, Janice ;
Kaplow, June ;
Luthman, Johan ;
Meibach, Richard ;
Raunig, David ;
Romero, Klaus ;
Samtani, Mahesh N. ;
Savage, Mary ;
Shaw, Leslie ;
Stephenson, Diane ;
Umek, Robert M. ;
Vanderstichele, Hugo ;
Willis, Brian ;
Yule, Susan .
JOURNAL OF ALZHEIMERS DISEASE, 2017, 55 (01) :19-35
[3]   AD molecular: Imaging tau aggregates with positron emissions tomography [J].
Betthauser, Tobey J. .
BRAIN IMAGING, 2019, 165 :107-138
[4]   In Vivo Characterization and Quantification of Neurofibrillary Tau PET Radioligand 18F-MK-6240 in Humans from Alzheimer Disease Dementia to Young Controls [J].
Betthauser, Tobey J. ;
Cody, Karly A. ;
Zammit, Matthew D. ;
Murali, Dhanabalan ;
Converse, Alexander K. ;
Barnhart, Todd E. ;
Stone, Charles K. ;
Rowley, Howard A. ;
Johnson, Sterling C. ;
Christian, Bradley T. .
JOURNAL OF NUCLEAR MEDICINE, 2019, 60 (01) :93-99
[5]   Advances and considerations in AD tau-targeted immunotherapy [J].
Bittar, Alice ;
Bhatt, Nemil ;
Kayed, Rakez .
NEUROBIOLOGY OF DISEASE, 2020, 134
[6]   Predicting clinical decline and conversion to Alzheimer's disease or dementia using novel Elecsys Aβ(1-42), pTau and tTau CSF immunoassays [J].
Blennow, Kaj ;
Shaw, Leslie M. ;
Stomrud, Erik ;
Mattsson, Niklas ;
Toledo, Jon B. ;
Buck, Katharina ;
Wahl, Simone ;
Eichenlaub, Udo ;
Lifke, Valeria ;
Simon, Maryline ;
Trojanowski, John Q. ;
Hansson, Oskar .
SCIENTIFIC REPORTS, 2019, 9 (1)
[7]   Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury [J].
Bogoslovsky, Tanya ;
Wilson, David ;
Chen, Yao ;
Hanlon, David ;
Gill, Jessica ;
Jeromin, Andreas ;
Song, Linan ;
Moore, Carol ;
Gong, Yunhua ;
Kenney, Kimbra ;
Diaz-Arrastia, Ramon .
JOURNAL OF NEUROTRAUMA, 2017, 34 (01) :66-73
[8]   [18F]GTP1 (Genentech Tau Probe 1), a radioligand for detecting neurofibrillary tangle tau pathology in Alzheimer's disease [J].
Bohorquez, Sandra Sanabria ;
Marik, Jan ;
Ogasawara, Annie ;
Tinianow, Jeff N. ;
Gill, Herman S. ;
Barret, Olivier ;
Tamagnan, Gilles ;
Alagille, David ;
Ayalon, Gai ;
Manser, Paul ;
Bengtsson, Thomas ;
Ward, Michael ;
Williams, Simon-Peter ;
Kerchner, Geoffrey A. ;
Seibyl, John P. ;
Marek, Kenneth ;
Weimer, Robby M. .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2019, 46 (10) :2077-2089
[9]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[10]   Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis [J].
Bridel, Claire ;
van Wieringen, Wessel N. ;
Zetterberg, Henrik ;
Tijms, Betty M. ;
Teunissen, Charlotte E. ;
Alvarez-Cermeno, Jose C. ;
Andreasson, Ulf ;
Axelsson, Markus ;
Backstrom, David C. ;
Bartos, Ales ;
Bjerke, Maria ;
Blennow, Kaj ;
Boxer, Adam ;
Brundin, Lou ;
Burman, Joachim ;
Christensen, Tove ;
Fialova, Lenka ;
Forsgren, Lars ;
Frederiksen, Jette L. ;
Gisslen, Magnus ;
Gray, Elizabeth ;
Gunnarsson, Martin ;
Hall, Sara ;
Hansson, Oskar ;
Herbert, Megan K. ;
Jakobsson, Joel ;
Jessen-Krut, Jan ;
Janelidze, Shorena ;
Johannsson, Gudmundur ;
Jonsson, Michael ;
Kappos, Ludwig ;
Khademi, Mohsen ;
Khalil, Michael ;
Kuhle, Jens ;
Landen, Mikael ;
Leinonen, Ville ;
Logroscino, Giancarlo ;
Lu, Ching-Hua ;
Lycke, Jan ;
Magdalinou, Nadia K. ;
Malaspina, Andrea ;
Mattsson, Niklas ;
Meeter, Lieke H. ;
Mehta, Sanjay R. ;
Modvig, Signe ;
Olsson, Tomas ;
Paterson, Ross W. ;
Perez-Santiago, Josue ;
Piehl, Fredrik ;
Pijnenburg, Yolande A. L. .
JAMA NEUROLOGY, 2019, 76 (09) :1035-1048