Biological markers of amyloid β-related mechanisms in Alzheimer's disease

被引：118
作者：
Hampel, Harald [2 ,3 ,4 ]
Shen, Yong [5 ]
Walsh, Dominic M. [6 ]
Aisen, Paul [7 ]
Shaw, Les M. [8 ]
Zetterberg, Henrik [1 ]
Trojanowski, John Q. [8 ]
Blennow, Kaj [1 ]
机构：
[1] Univ Gothenburg, Sahlgrenska Acad, Clin Neurochem Lab, Inst Neurosci & Physiol,Dept Psychiat & Neurochem, SE-43180 Molndal, Sweden
[2] Adelaide & Meath Hosp Incorporating Natl Children, Trinity Coll dublin, Trinity Ctr Hlth Sci, Discipline Psychiat,Sch Med, Dublin, Ireland
[3] Adelaide & Meath Hosp Incorporating Natl Children, TCIN, Lab Neuroimaging & Biomarker Res, Dublin, Ireland
[4] Univ Munich, Dept Psychiat, Alzheimers Mem Ctr, D-8000 Munich, Germany
[5] Sun Hlth Res Inst, Haldeman Lab Mol & Cellular Neurobiol, Sun City, AZ USA
[6] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Lab Neurodegenerat Res, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland
[7] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA
[8] Univ Penn, Sch Med, Dept Pathol & Lab Med, Inst Aging,Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
来源：
EXPERIMENTAL NEUROLOGY | 2010年 / 223卷 / 02期
基金：
爱尔兰科学基金会; 瑞典研究理事会;
关键词：
Alzheimer's disease (AD); Alzheimer's Disease Neuroimaging Initiative (ADNI); Amyloid beta-peptide (A beta); Amyloid precursor protein (APP); Biochemical markers; Biomarkers; beta-Site APP-cleaving enzyme 1 (BACE1); Cerebrospinal fluid (CSF); Diagnosis; Drug development; Mild cognitive impairment (MCI); Mechanism of action; Neurochemistry; Oligomers; Plasma; Pre-clinical; Prediction; Presymptomatic; Stratification; US Food and Drug Administration (FDA); European Medicines Agency (EMEA); MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID LEVELS; GAMMA-SECRETASE INHIBITOR; AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; TEMPORAL-LOBE ATROPHY; YOUNG PLAQUE-FREE; PRECURSOR PROTEIN; A-BETA; CSF BIOMARKERS;
D O I：
10.1016/j.expneurol.2009.09.024
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer's disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (A beta) production and aggregation. In drug development, it is important to co-develop biomarkers for A beta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include A beta isoforms (A beta 40/A beta 42), soluble APP isoforms, A beta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma A beta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码：334 / 346
页数：13
相关论文
共 166 条
  • [1] Alzheimers Assoc, 1998, NEUROBIOL AGING, V19, P109
  • [2] Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment
    Andreasen, N
    Minthon, L
    Vanmechelen, E
    Vanderstichele, H
    Davidsson, P
    Winblad, B
    Blennow, K
    [J]. NEUROSCIENCE LETTERS, 1999, 273 (01) : 5 - 8
  • [3] Cerebrospinal fluid β-amyloid(1-42) in Alzheimer disease -: Differences between early- and late-onset Alzheimer disease and stability during the course of disease
    Andreasen, N
    Hesse, C
    Davidsson, P
    Minthon, L
    Wallin, A
    Winblad, B
    Vanderstichele, H
    Vanmechelen, E
    Blennow, K
    [J]. ARCHIVES OF NEUROLOGY, 1999, 56 (06) : 673 - 680
  • [4] Aspects of β-amyloid as a biomarker for Alzheimer's disease
    Andreasson, Ulf
    Portelius, Erik
    Andersson, Malin E.
    Blennow, Kaj
    Zetterberg, Henrik
    [J]. BIOMARKERS IN MEDICINE, 2007, 1 (01) : 59 - 78
  • [5] The functions of mammalian amyloid precursor protein and related amyloid precursor-like proteins
    Anliker, Brigitte
    Mueller, Ulrike
    [J]. NEURODEGENERATIVE DISEASES, 2006, 3 (4-5) : 239 - 246
  • [6] Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease
    Bard, F
    Cannon, C
    Barbour, R
    Burke, RL
    Games, D
    Grajeda, H
    Guido, T
    Hu, K
    Huang, JP
    Johnson-Wood, K
    Khan, K
    Kholodenko, D
    Lee, M
    Lieberburg, I
    Motter, R
    Nguyen, M
    Soriano, F
    Vasquez, N
    Weiss, K
    Welch, B
    Seubert, P
    Schenk, D
    Yednock, T
    [J]. NATURE MEDICINE, 2000, 6 (08) : 916 - 919
  • [7] Presenilin clinical mutations can affect γ-secretase activity by different mechanisms
    Bentahir, M
    Nyabi, O
    Verhamme, J
    Tolia, A
    Horré, K
    Wiltfang, J
    Esselmann, H
    De Strooper, B
    [J]. JOURNAL OF NEUROCHEMISTRY, 2006, 96 (03) : 732 - 742
  • [8] Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: Prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine
    Blasko, Imrich
    Jellinger, Kurt
    Kemmler, Georg
    Krampla, Wolfgang
    Jungwirth, Susanne
    Wichart, Ildigo
    Tragl, Karl Heinz
    Fischer, Peter
    [J]. NEUROBIOLOGY OF AGING, 2008, 29 (01) : 1 - 11
  • [9] CSF markers for incipient Alzheimer's disease
    Blennow, K
    Hampel, H
    [J]. LANCET NEUROLOGY, 2003, 2 (10) : 605 - 613
  • [10] tau protein in cerebrospinal fluid - A biochemical marker for axonal degeneration in Alzheimer disease?
    Blennow, K
    Wallin, A
    Agren, H
    Spenger, C
    Siegfried, J
    Vanmechelen, E
    [J]. MOLECULAR AND CHEMICAL NEUROPATHOLOGY, 1995, 26 (03) : 231 - 245
12345678910