Reliable Measurements of the β-Amyloid Pool in Blood Could Help in the Early Diagnosis of AD

Overview

Journal Int J Alzheimers Dis

Publisher Wiley

Date 2012 Sep 8

PMID 22957297

Citations 34

Authors

Pedro Pesini

Virginia Perez-Grijalba

Inmaculada Monleon

Merce Boada

Lluis Tarraga

Pablo Martinez-Lage

Itziar San-Jose

Manuel Sarasa

Affiliations

Soon will be listed here.

Abstract

The present study was aimed at assessing the capability of Aβ1-40 and Aβ1-42 levels in undiluted plasma (UP), diluted plasma (DP), and cell bound (CB) to distinguish between early stages of Alzheimer's disease (AD), amnesic mild cognitive impairment (MCI), and healthy control (HC). Four blood samples from each participant were collected during one month and the levels of Aβ1-40 and Aβ1-42 were determined by a blinded proprietary ELISA sandwich (Araclon Biotech. Zaragoza, Spain). First striking result was that the amount of Aβ1-40 and Aβ1-42 in UP represented only a small proportion (~15%) of the total beta-amyloid pool in blood (βAPB) described here as the sum of Aβ1-40 and Aβ1-42 in blood where they are free in plasma, bound to plasma proteins, and bound to blood cells. Furthermore, we found that levels of Aβ1-40 and Aβ1-42 in UP, DP, and CB were significantly higher in MCI when compared to HC. On average, the total βAPB was 1.8 times higher in MCI than in HC (P = 0.03) and allowed to discriminate between MCI and HC with a sensitivity and specificity over 80%. Thus, quantification of several markers of the βAPB could be useful and reliable in the discrimination between MCI and HC.

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References

Hampel H, Burger K, Teipel S, Bokde A, Zetterberg H, Blennow K . Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimers Dement. 2008; 4(1):38-48. DOI: 10.1016/j.jalz.2007.08.006. View

Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E . Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment. Neurobiol Aging. 2008; 31(3):357-67. DOI: 10.1016/j.neurobiolaging.2008.03.027. View

Graff-Radford N, Crook J, Lucas J, Boeve B, Knopman D, Ivnik R . Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol. 2007; 64(3):354-62. DOI: 10.1001/archneur.64.3.354. View

Blennow K, Hampel H, Weiner M, Zetterberg H . Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010; 6(3):131-44. DOI: 10.1038/nrneurol.2010.4. View

Alegret M, Boada-Rovira M, Vinyes-Junque G, Valero S, Espinosa A, Hernandez I . Detection of visuoperceptual deficits in preclinical and mild Alzheimer's disease. J Clin Exp Neuropsychol. 2009; 31(7):860-7. PMC: 2834652. DOI: 10.1080/13803390802595568. View

Schupf N, Tang M, Fukuyama H, Manly J, Andrews H, Mehta P . Peripheral Abeta subspecies as risk biomarkers of Alzheimer's disease. Proc Natl Acad Sci U S A. 2008; 105(37):14052-7. PMC: 2544577. DOI: 10.1073/pnas.0805902105. View

Freeman S, Raju S, Hyman B, Frosch M, Irizarry M . Plasma Abeta levels do not reflect brain Abeta levels. J Neuropathol Exp Neurol. 2007; 66(4):264-71. DOI: 10.1097/NEN.0b013e31803d3ae4. View

Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M . CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009; 302(4):385-93. DOI: 10.1001/jama.2009.1064. View

Lopez O, Kuller L, Mehta P, Becker J, Gach H, Sweet R . Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study. Neurology. 2008; 70(19):1664-71. PMC: 2670993. DOI: 10.1212/01.wnl.0000306696.82017.66. View

10.

Fagan A, Head D, Shah A, Marcus D, Mintun M, Morris J . Decreased cerebrospinal fluid Abeta(42) correlates with brain atrophy in cognitively normal elderly. Ann Neurol. 2009; 65(2):176-83. PMC: 2763631. DOI: 10.1002/ana.21559. View

11.

Zetterberg H . Is plasma amyloid-beta a reliable biomarker for Alzheimer's disease?. Recent Pat CNS Drug Discov. 2008; 3(2):109-11. DOI: 10.2174/157488908784534595. View

12.

Cedazo-Minguez A, Winblad B . Biomarkers for Alzheimer's disease and other forms of dementia: clinical needs, limitations and future aspects. Exp Gerontol. 2009; 45(1):5-14. DOI: 10.1016/j.exger.2009.09.008. View

13.

Deane R, Bell R, Sagare A, Zlokovic B . Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol Disord Drug Targets. 2009; 8(1):16-30. PMC: 2872930. DOI: 10.2174/187152709787601867. View

14.

Hixson J, Vernier D . Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990; 31(3):545-8. View

15.

Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein H, Vermersch P . Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992; 55(10):967-72. PMC: 1015202. DOI: 10.1136/jnnp.55.10.967. View

16.

Biere A, Ostaszewski B, Stimson E, Hyman B, Maggio J, Selkoe D . Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma. J Biol Chem. 1996; 271(51):32916-22. DOI: 10.1074/jbc.271.51.32916. View

17.

Lewczuk P, Kornhuber J, Vanderstichele H, Vanmechelen E, Esselmann H, Bibl M . Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: a multicenter study. Neurobiol Aging. 2007; 29(6):812-8. DOI: 10.1016/j.neurobiolaging.2006.12.010. View

18.

Schupf N, Patel B, Pang D, Zigman W, Silverman W, Mehta P . Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome. Arch Neurol. 2007; 64(7):1007-13. PMC: 2587094. DOI: 10.1001/archneur.64.7.1007. View

19.

Zlokovic B . Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci. 2005; 28(4):202-8. DOI: 10.1016/j.tins.2005.02.001. View

20.

Hansson O, Zetterberg H, Buchhave P, Andreasson U, Londos E, Minthon L . Prediction of Alzheimer's disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2007; 23(5):316-20. DOI: 10.1159/000100926. View