Plasma Aβ42/40 Ratio Detects Early Stages of Alzheimer’s Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study
- 12 Downloads
Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer’s disease (AD) in large population screening strategies.
This study evaluated the potential of plasma β-amyloid (Aβ) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years.
Total plasma Aβ42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern.
Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a highrisk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF).
TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.
Key wordsβ-amyloid (Aβ) Alzheimer’s disease plasma biomarker Aβ ratio
- 5.Sperling RA, Rentz DM, Johnson KA, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med 2014 Mar;%19;6:228fs13.Google Scholar
- 6.Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011 May;7:270–279.Google Scholar
- 7.Bohnen NI, Djang DS, Herholz K, Anzai Y, Minoshima S. Effectiveness and safety of 18F–FDG PET in the evaluation of dementia: a review of the recent literature. J Nucl Med 2012 Jan;53:59–71.Google Scholar
- 9.Weiner MW, Veitch DP, Aisen PS, et al. The Alzheimer’s Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimers Dement 2012 Feb;8:S1–68.Google Scholar
- 10.Rowe CC, Bourgeat P, Ellis KA, et al. Predicting Alzheimer disease with beta–amyloid imaging: results from the Australian imaging, biomarkers, and lifestyle study of ageing. Ann Neurol 2013 Dec;74:905–913.Google Scholar
- 11.Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement 2015 Jan;11:58–69.Google Scholar
- 12.Hansson O, Zetterberg H, Vanmechelen E, et al. Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging 2010 Mar;31:357–367.Google Scholar
- 14.Lovheim H, Elgh F, Johansson A, et al. Plasma concentrations of free amyloidbeta cannot predict the development of Alzheimer’s disease. Alzheimers Dement 2016 Sep 28;10.Google Scholar
- 15.Cosentino SA, Stern Y, Sokolov E, et al. Plasma beta–Amyloid and Cognitive Decline. Arch Neurol 2010 Aug 9.Google Scholar
- 17.Chouraki V, Beiser A, Younkin L, et al. Plasma amyloid–beta and risk of Alzheimer’s disease in the Framingham Heart Study. Alzheimers Dement 2015 Mar;11:249–257.Google Scholar
- 18.Graff–Radford NR, Crook JE, Lucas J, et al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol 2007 Mar;64:354–362.Google Scholar
- 20.Fandos N, Perez–Grijalba V, Pesini P, et al. Plasma amyloid beta 42/40 ratios as biomarkers for amyloid beta cerebral deposition in cognitively normal individuals. Alzheimers Dement (Amst) 2017 Sep 12;8:179–187. doi: 10.1016/j. dadm.2017.07.004. eCollection;%2017.:179–187.Google Scholar
- 21.Ovod V, Ramsey KN, Mawuenyega KG, et al. Amyloid beta concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 2017 Aug;13:841–849.Google Scholar
- 23.Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment, 4th Edition ed. New York: Oxofrd University Press, 2004.Google Scholar
- 24.Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004 Sep;256:183–194.Google Scholar
- 25.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Edition ed. Washington D.C.: American Psychiatric Association, 2000.Google Scholar
- 28.Nordberg A, Carter SF, Rinne J, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2013 Jan;40:104–114.Google Scholar
- 31.Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990 Mar;31:545–548.Google Scholar
- 32.van OM, Hofman A, Soares HD, Koudstaal PJ, Breteler MM. Plasma Abeta(1–40) and Abeta(1–42) and the risk of dementia: a prospective case–cohort study. Lancet Neurol 2006 Aug;5:655–660.Google Scholar
- 33.Abdullah L, Luis C, Paris D, et al. Serum Abeta levels as predictors of conversion to mild cognitive impairment/Alzheimer disease in an ADAPT subcohort. Mol Med 2009 Nov;15:432–437.Google Scholar
- 34.Yaffe K, Weston A, Graff–Radford NR, et al. Association of plasma betaamyloid level and cognitive reserve with subsequent 19;305:261–266.Google Scholar
- 35.Okereke OI, Xia W, Selkoe DJ, Grodstein F. Ten–year change in plasma amyloid beta levels and late–life cognitive decline. Arch Neurol 2009 Oct;66:1247–1253.Google Scholar
- 36.Koyama A, Okereke OI, Yang T, Blacker D, Selkoe DJ, Grodstein F. Plasma amyloid–beta as a predictor of dementia and cognitive decline: a systematic review and meta–analysis. Arch Neurol 2012 Jul;69:824–831.Google Scholar
- 39.Shaw LM, Vanderstichele H, Knapik–Czajka M, et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 2009 Apr;65:403–413.Google Scholar
- 40.Toledo JB, Vanderstichele H, Figurski M, et al. Factors affecting Abeta plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol 2011 Oct;122:401–413.Google Scholar
- 41.Vanderstichele H, Van KE, Hesse C, et al. Standardization of measurement of beta–amyloid(1–42) in cerebrospinal fluid and plasma. Amyloid 2000 Dec;7:245–258.Google Scholar
- 42.Roher AE, Esh CL, Kokjohn TA, et al. Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease. Alzheimers Dement 2009 Jan;5:18–29.Google Scholar
- 44.Figurski MJ, Waligorska T, Toledo J, et al. Improved protocol for measurement of plasma beta–amyloid in longitudinal evaluation of Alzheimer’s Disease Neuroimaging Initiative study patients. Alzheimers Dement 2012 Jul;8:250–260.Google Scholar
- 45.Insel PS, Mattsson N, Mackin RS, et al. Biomarkers and cognitive endpoints to optimize trials in Alzheimer’s disease. Ann Clin Transl Neurol 2015 May;2:534–547.Google Scholar