TY - JOUR
T1 - Current state of Alzheimer’s fluid biomarkers
AU - Molinuevo, José Luis
AU - Ayton, Scott
AU - Batrla, Richard
AU - Bednar, Martin M.
AU - Bittner, Tobias
AU - Cummings, Jeffrey
AU - Fagan, Anne M.
AU - Hampel, Harald
AU - Mielke, Michelle M.
AU - Mikulskis, Alvydas
AU - O’bryant, Sid
AU - Scheltens, Philip
AU - Sevigny, Jeffrey
AU - Shaw, Leslie M.
AU - Soares, Holly D.
AU - Tong, Gary
AU - Trojanowski, John Q.
AU - Zetterberg, Henrik
AU - Blennow, Kaj
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2018/12
Y1 - 2018/12
N2 - Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/ adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.
AB - Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/ adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.
KW - Alzheimer’s disease
KW - Amyloid
KW - Biomarker
KW - Blood
KW - Cerebrospinal fluid
KW - Tau
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U2 - 10.1007/s00401-018-1932-x
DO - 10.1007/s00401-018-1932-x
M3 - Article
C2 - 30488277
AN - SCOPUS:85057564709
SN - 0001-6322
VL - 136
SP - 821
EP - 853
JO - Acta neuropathologica
JF - Acta neuropathologica
ER -