Plasma amyloid-beta as a biomarker in Alzheimer's disease: the AIBL study of aging.

Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Abeta as an AD biomarker and its relationship with Abeta load and to determine the effect of different assay methods on the interpretation of Abeta levels. Plasma Abeta1-40, Abeta1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Abeta levels were compared to Abeta load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Abeta1-42 and Abeta1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Abeta load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Abeta isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Abeta has diagnostic value in a panel of biomarkers.

[1]  F. Jessen,et al.  Amyloid β peptides in plasma in early diagnosis of Alzheimer's disease: A multicenter study with multiplexing , 2010, Experimental Neurology.

[2]  Anders Wallin,et al.  Evaluation of plasma Aβ40 and Aβ42 as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment , 2010, Neurobiology of Aging.

[3]  P. Deyn,et al.  No correlation between time-linked plasma and CSF Aβ levels , 2009, Neurochemistry International.

[4]  L. Buée,et al.  Association of plasma amyloid β with risk of dementia , 2009, Neurology.

[5]  C. Rowe,et al.  The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease , 2009, International Psychogeriatrics.

[6]  W. M. van der Flier,et al.  CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. , 2009, JAMA.

[7]  A. Drzezga,et al.  Beta Amyloid in Alzheimer's Disease: Increased Deposition in Brain Is Reflected in Reduced Concentration in Cerebrospinal Fluid , 2009, Biological Psychiatry.

[8]  M Schwaiger,et al.  Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease , 2009, Neurology.

[9]  G. Alexander,et al.  Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease , 2009, Proceedings of the National Academy of Sciences.

[10]  R. Petersen,et al.  Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects , 2009, Annals of neurology.

[11]  A. Fagan,et al.  Decreased cerebrospinal fluid Aβ42 correlates with brain atrophy in cognitively normal elderly , 2009, Annals of neurology.

[12]  C. Adler,et al.  Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease , 2009, Alzheimer's & Dementia.

[13]  Sébastien Ourselin,et al.  Appearance modeling of 11C PiB PET images: Characterizing amyloid deposition in Alzheimer's disease, mild cognitive impairment and healthy aging , 2008, NeuroImage.

[14]  H. Engler,et al.  PET imaging of amyloid deposition in patients with mild cognitive impairment , 2008, Neurobiology of Aging.

[15]  H. Fukuyama,et al.  Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease , 2008, Proceedings of the National Academy of Sciences.

[16]  T. Cowie,et al.  The apolipoprotein E epsilon4 allele is not associated with cognitive dysfunction in cardiac surgery. , 2008, The Annals of thoracic surgery.

[17]  J. Becker,et al.  Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study , 2008, Neurology.

[18]  B. Hyman,et al.  Plasma Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men , 2008 .

[19]  Georg Kemmler,et al.  Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: Prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine , 2008, Neurobiology of Aging.

[20]  V. Mathura,et al.  The influence of diagnosis, intra- and inter-person variability on serum and plasma Aβ levels , 2007, Neuroscience Letters.

[21]  Paul Maruff,et al.  β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease , 2007 .

[22]  C. Rowe,et al.  Imaging β-amyloid burden in aging and dementia , 2007, Neurology.

[23]  Henrik Zetterberg,et al.  Prediction of Alzheimer’s Disease Using the CSF Aβ42/Aβ40 Ratio in Patients with Mild Cognitive Impairment , 2007, Dementia and Geriatric Cognitive Disorders.

[24]  R. Petersen,et al.  Association of Low Plasma Aβ42/Aβ40 Ratios With Increased Imminent Risk for Mild Cognitive Impairment and Alzheimer Disease , 2007 .

[25]  A. Hofman,et al.  Plasma Aβ1–40 and Aβ1–42 and the risk of dementia: a prospective case-cohort study , 2006, The Lancet Neurology.

[26]  C. Mathers,et al.  Global prevalence of dementia: a Delphi consensus study , 2005, The Lancet.

[27]  Victoria M Perreau,et al.  Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease , 2005, The Journal of Neuroscience.

[28]  M. Inglese,et al.  Plasma levels of amyloid β-protein 42 are increased in women with mild cognitive impairment , 2004, Neurology.

[29]  C. Jack,et al.  Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment , 2004, Journal of internal medicine.

[30]  J. Growdon,et al.  Age but Not Diagnosis Is the Main Predictor of Plasma Amyloid β-Protein Levels , 2003 .

[31]  Chester A. Mathis,et al.  A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. , 2002, Bioorganic & medicinal chemistry letters.

[32]  W. Klunk,et al.  Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. , 2001, Life sciences.

[33]  P. Mehta,et al.  Amyloid β protein 1–40 and 1–42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease , 2001, Neuroscience Letters.

[34]  D. Salmon,et al.  Cognitive screening and neuropsychological assessment in early Alzheimer's disease. , 2001, Clinics in geriatric medicine.

[35]  K. Blennow,et al.  Standardization of measurement of β-amyloid(1-42) in cerebrospinal fluid and plasma , 2000, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[36]  H. Wiśniewski,et al.  Plasma amyloid β‐peptide 1–42 and incipient Alzheimer's disease , 1999 .

[37]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[38]  T. Iwatsubo.  Amyloid β Protein in Plasma as a Diagnostic Marker for Alzheimer’s Disease , 1998, Neurobiology of Aging.

[39]  G. Schellenberg,et al.  Secreted amyloid β–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 , 1996, Nature Medicine.

[40]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[41]  D. Cox,et al.  An Analysis of Transformations , 1964 .

[42]  H. Wiśniewski,et al.  Plasma and cerebrospinal fluid Levels of amyloid β proteins 1-40 and 1-42 in Alzheimer disease , 2000 .