Original Paper

Acta Neuropathologica

, Volume 122, Issue 4, pp 401-413

Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI

  • Jon B. ToledoAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine
  • , Hugo VandersticheleAffiliated withDepartment of Diagnostic Development, Innogenetics NV
  • , Michal FigurskiAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine
  • , Paul S. AisenAffiliated withUniversity of California at San Diego
  • , Ronald C. PetersenAffiliated withMayo Clinic College of Medicine
  • , Michael W. WeinerAffiliated withDepartment of Radiology Medicine and Psychiatry, University of California at San Francisco
  • , Clifford R. JackJrAffiliated withMayo Clinic
  • , William JagustAffiliated withHelen Wills Neuroscience Institute University of California
  • , Charles DecarliAffiliated withDepartment of Neurology, University of California
    • , Arthur W. TogaAffiliated withLaboratory of Neuro Imaging, Department of Neurology, University of California at Los Angeles School of Medicine
    • , Estefanía ToledoAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of MedicineDepartment of Preventive Medicine and Public Health, Medical School, Clinica Universidad de Navarra, University of Navarra
    • , Sharon X. XieAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of MedicineDepartment of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine
    • , Virginia M.-Y. LeeAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine
    • , John Q. TrojanowskiAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine Email author 
    • , Leslie M. ShawAffiliated withDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine Email author 

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Abstract

Previous studies of Aβ plasma as a biomarker for Alzheimer’s disease (AD) obtained conflicting results. We here included 715 subjects with baseline Aβ1-40 and Aβ1-42 plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and Aβ1-42 measures in cerebrospinal fluid (CSF). Association between Aβ and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma Aβ. The effect of age differed according to AD stage. Plasma Aβ1-42 showed mild correlation with other biomarkers of Aβ pathology and were associated with infarctions in MRI. Longitudinal measurements of Aβ1-40 and Aβ1-42 plasma levels showed modest value as a prognostic factor for clinical progression. Our longitudinal study of complementary measures of Aβ pathology (PIB, CSF and plasma Aβ) and other biomarkers in a cohort with an extensive neuropsychological battery is significant because it shows that plasma Aβ measurements have limited value for disease classification and modest value as prognostic factors over the 3-year follow-up. However, with longer follow-up, within subject plasma Aβ measurements could be used as a simple and minimally invasive screen to identify those at increased risk for AD. Our study emphasizes the need for a better understanding of the biology and dynamics of plasma Aβ as well as the need for longer term studies to determine the clinical utility of measuring plasma Aβ.

Keywords

Biomarker Alzheimer disease Amyloid beta-peptides Prognosis Diagnosis PET Cerebrospinal fluid