The AD-CSF-index discriminates Alzheimer's disease patients from healthy controls: a validation study.

Molinuevo, Jose L; Gispert, Juan Domingo; Dubois, Bruno; HENEKA, Michael; Lleo, Alberto; Engelborghs, Sebastiaan; Pujol, Jesús; de Souza, Leonardo Cruz; Alcolea, Daniel; Jessen, Frank; Sarazin, Marie; Lamari, Foudil; Balasa, Mircea; Antonell, Anna; Rami, Lorena

doi:10.3233/JAD-130203

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The AD-CSF-index discriminates Alzheimer's disease patients from healthy controls: a validation study.

Molinuevo, Jose L; Gispert, Juan Domingo; Dubois, Bruno et al.

2013 • In Journal of Alzheimer's Disease, 36 (1), p. 67 - 77

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https://hdl.handle.net/10993/60946

DOI
10.3233/JAD-130203

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23524657

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Keywords :

Amyloid beta-Peptides; Biomarkers; Peptide Fragments; amyloid beta-protein (1-42); tau Proteins; Aged; Alzheimer Disease/cerebrospinal fluid; Alzheimer Disease/diagnosis; Amyloid beta-Peptides/cerebrospinal fluid; Biomarkers/cerebrospinal fluid; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Peptide Fragments/cerebrospinal fluid; Sensitivity and Specificity; tau Proteins/cerebrospinal fluid; Alzheimer's disease; cerebrospinal fluid; diagnostic accuracy; sensitivity; specificity; Neuroscience (all); Clinical Psychology; Geriatrics and Gerontology; Psychiatry and Mental Health; General Medicine; General Neuroscience

Abstract :

[en] [en] BACKGROUND: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) show an acceptable diagnostic sensitivity and specificity; however, their interpretation and ease of use is far from optimal. OBJECTIVE: To study and validate the diagnostic accuracy of an easy-to-use normalized CSF biomarker index, the AD-CSF-index, in different European populations. METHODS: A total of 342 subjects, 103 healthy controls and 239 AD patients, from four European memory clinics were included. The AD-CSF-index was constructed from the addition of normalized values between the minimum and maximum of amyloid and tau protein levels. The diagnostic accuracy, receiver operating characteristic, and regression analysis of the AD-CSF-index and other composite indices were evaluated in this study. RESULTS: AD patients presented a significantly higher AD-CSF-index than healthy subjects (control = 0.5204; AD = 1.2272; p < 0.001). The AD-CSF-index obtained a sensitivity of 88.6% at 85% specificity and also showed a significantly higher diagnostic power (p < 0.05) than the individual CSF biomarkers and other studied indices. The performance of the AD-CSF-index was very similar between ELISA and MesoScale measurements. Cut-off values of approximately 0.75 provided the lowest achievable overall classification errors and a cut-off point of about 0.95 consistently provided specificities above 85%. CONCLUSION: The AD-CSF-index represents a novel approach, combining normalized CSF values, for the biological diagnosis of AD. The AD-CSF-index presents an optimal AUC with high sensitivity and specificity and seems to be a simple and intuitive way to interpret AD CSF biomarker results even from different analytical platforms.

Disciplines :

Neurology

Author, co-author :

Molinuevo, Jose L; Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain. jlmoli@clinic.ub.es

Gispert, Juan Domingo; BarcelonaBeta Brain Research Centre, Pasqual Maragall Foundation, Barcelona, Spain

Dubois, Bruno; Alzheimer Institute, Research and Resource Memory Centre, Pitié-Salpêtriére Hospital, Paris, France

HENEKA, Michael ; Neurology Department, University of Bonn, Germany

Lleo, Alberto; Neurology Department, Hospital Sant Pau, CIBERNED, Barcelona, Spain

Engelborghs, Sebastiaan; Reference Centre for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium

Pujol, Jesús; CRC-Mar, Hospital Del Mar, CRC Corporació Sanitària, Barcelona, Spain

de Souza, Leonardo Cruz; Alzheimer Institute, Research and Resource Memory Centre, Pitié-Salpêtriére Hospital, Paris, France

Alcolea, Daniel; Neurology Department, Hospital Sant Pau, CIBERNED, Barcelona, Spain

Jessen, Frank; Department of Psychiatry, University of Bonn, Bonn, Germany

More authors (5 more)

External co-authors :

yes

Language :

English

Title :

The AD-CSF-index discriminates Alzheimer's disease patients from healthy controls: a validation study.

Publication date :

2013

Journal title :

Journal of Alzheimer's Disease

ISSN :

1387-2877

eISSN :

1875-8908

Publisher :

IOS Press, Amsterdam, Netherlands

Volume :

Issue :

Pages :

67 - 77

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://content.iospress.com/download?id=10.3233/JAD-130203

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Bibliography

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr., Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia 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 7, 263-269.
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ; Alzheimer's Disease Neuroimaging, Initiative (2009) Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 65, 403-413.
Engelborghs S, De Vreese K, Van de Casteele T, Vanderstichele H,Van Everbroeck B, Cras P, Martin JJ,Vanmechelen E, De Deyn PP (2008) Diagnostic performance of a CSFbiomarker panel in autopsy-confirmed dementia. Neurobiol Aging 29, 1143-1159.
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G,Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P (2007) Research criteria for the diagnosis of Alzheimer's disease: Revising the NINCDS-ADRDA criteria. Lancet Neurol 6, 734-746.
Rami L, Solé-Padullés C, Fortea J, Bosch B, Lladó A, Antonell A, Olives J, Castellví M, Bartres-Faz D, Sánchez-Valle R, Molinuevo JL (2012) Applying the new research diagnostic criteria: MRI findings and neuropsychological correlations of prodromal AD. Int J Geriatr Psychiatry 27, 127-134.
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ; Alzheimer's Disease Neuroimaging Initiative. (2009) Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 65, 403-413.
Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, Bergeson J, Manetti GJ, Zimmermann M, Tang B, Bartko JJ, Cohen RM (2003) Decreased-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. J Am Med Assoc 289, 2094-2103.
Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M,DeDeyn PP, Bancher C, Cras P,Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H (1999) Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology 52, 1555-1562.
Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, Bergeson J, Manetti GJ, Zimmermann M, Tang B, Bartko JJ, Cohen RM (2003) Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 289, 2094-2103.
Blennow K, Vanmechelen E (1998) Combination of the different biological markers for increasing specificity of in vivo Alzheimer's testing. J Neural Transm Suppl 53, 223-235.
Shoji M, Matsubara E, Kanai M, Watanabe M, Nakamura T, Tomidokoro Y, Shizuka M, Wakabayashi K, Igeta Y, Ikeda Y, Mizushima K, Amari M, Ishiguro K, Kawarabayashi T, Harigaya Y, Okamoto K, Hirai S (1998) Combination assay of CSF tau, A beta 1-40 and A beta 1-42(43) as a biochemical marker of Alzheimer's disease. J Neurol Sci 158, 134-140.
Maddalena A, Papassotiropoulos A, Müller-Tillmanns B, Jung HH, Hegi T, Nitsch RM, Hock C (2003) Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to betaamyloid peptide42. Arch Neurol 60, 1202-1206.
Riemenschneider M, Lautenschlager N, Wagenpfeil S, Diehl J, Drzezga A,KurzA(2002) Cerebrospinal fluid tau and betaamyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. Arch Neurol 59, 1729-1734.
Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, Coart E, Morris JC, Holtzman DM (2011) Comparison of analytical platforms for cerebrospinal fluid measures of-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol 68, 1137-1144.
Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM (2007) Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64, 343-349.
Visser PJ, Verhey F, Knol DL, Mintun MA,Morris JC, Holtzman DM (2009) Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: A prospective cohort study. Lancet Neurol 8, 619-627.
Craig-Schapiro R, Kuhn M, Xiong C, Pickering EH, Liu J, Misko TP, Perrin RJ, Bales KR, Soares H, Fagan AM, Holtzman DM (2011) Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer's disease diagnosis and prognosis. PLoS One 6, e18850.
Molinuevo JL, Gispert JD, Pujol J, Rojas S, Lladó A, Balasa M, Antonell A, Sánchez-Valle R, Rami L (2012) A new approach to the Alzheimer's disease diagnosis with biomarkers: Description of the AD-CSF-index. Rev Neurol 54, 513-522.
Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, Bocchio-Chiavetto L, Blankenstein MA, Carrillo MC, Chalbot S, Coart E, Chiasserini D, Cutler N, Dahlfors G, Duller S, Fagan AM, Forlenza O, Frisoni GB, Galasko D, Galimberti D, Hampel H, Handberg A, Heneka MT, Herskovits AZ, Herukka SK, Holtzman DM, Humpel C, Hyman BT, Iqbal K, Jucker M, Kaeser SA, Kaiser E, Kapaki E, Kidd D, Klivenyi P, Knudsen CS, Kummer MP, Lui J, Lladó A, Lewczuk P, Li QX, Martins R, Masters C, McAuliffe J, Mercken M, Moghekar A, Molinuevo JL, Montine TJ, Nowatzke W, O'Brien R, Otto M, Paraskevas GP, Parnetti L, Petersen RC, Prvulovic D, de Reus HP, Rissman RA, Scarpini E, Stefani A, Soininen H, Schröder J, Shaw LM, Skinningsrud A, Skrogstad B, Spreer A, Talib L, Teunissen C, Trojanowski JQ, Tumani H, Umek RM, Van Broeck B, Vanderstichele H, Vecsei L, Verbeek MM,Windisch M, Zhang J, Zetterberg H, Blennow K (2011) The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement 7, 386-395.e6.
Schipke CG, Prokop S, Heppner FL, Heuser I, PetersO(2011) Comparison of immunosorbent assays for the quantification of biomarkers for Alzheimer's disease in human cerebrospinal fluid. Dement Geriatr Cogn Disord 31, 139-145.
Hort J, O'Brien JT, Gainotti G, Pirttila T, Popescu BO, Rektorova I, Sorbi S, Scheltens P, Scientist Panel on EFNS, Dementia (2010) EFNS guidelines for the diagnosis and management of Alzheimer's disease. Eur J Neurol 17, 1236-1248.
Galasko D, Chang L, Motter R, Clark CM, Kaye J, Knopman D, Thomas R, Kholodenko D, Schenk D, Lieberburg I, Miller B, Green R, Basherad R, Kertiles L, Boss MA, Seubert P (1998) High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. Arch Neurol 55, 937-945.
Lewczuk P, Zimmermann R, Wiltfang J, Kornhuber J (2009) Neurochemical dementiadiagnostics: A simple algorithm for interpretation of the CSF biomarkers. J Neural Transm 116, 1163-1167.
Li G, Sokal I, Quinn JF, Leverenz JB, Brodey M, Schellenberg GD, Kaye JA, Raskind MA, Zhang J, Peskind ER, Montine TJ (2007) CSF tau/Abeta42 ratio for increased risk of mild cognitive impairment: A follow-up study. Neurology 69, 631-639.
The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group (1998) Consensus report of the Working Group on: Molecular and Biochemical Markers of Alzheimer's Disease. Neurobiol Aging 19, 109-116.
Jack CR Jr., Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 9, 119-128.
Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P (2010) Revising the definition of Alzheimer's disease: A new lexicon. Lancet Neurol 9, 1118-1127.
Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 280-292.
Rami L, Fortea J, Bosch B, Solé-Padullés C, Lladó A, Iranzo A, Sánchez-Valle R, Molinuevo JL (2011) Cerebrospinal fluid biomarkers and memory present distinct associations along the continuum from healthy subjects to AD patients. J Alzheimers Dis 23, 319-326.
Jack CR Jr., Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Lowe V, Kantarci K, Bernstein MA, Senjem ML, Gunter JL, Boeve BF, Trojanowski JQ, Shaw LM, Aisen PS,Weiner MW, Petersen RC, Knopman DS; Alzheimer's Disease Neuroimaging Initiative (2012) Shapes of the trajectories of 5 major biomarkers of Alzheimer disease. Arch Neurol 69, 856-867.
Bouwman FH, Verwey NA, Klein M, Kok A, Blankenstein MA, Sluimer JD, Barkhof F, van der Flier WM, Scheltens P (2010) New research criteria for the diagnosis of Alzheimer's disease applied in a memory clinic population. Dement Geriatr Cogn Disord 30, 1-7.
Galluzzi S, Ghidoni R, Paghera B, Amicucci G, Bonetti M, Zanetti O, Cotelli M, Gennarelli M, Frisoni GB; Translational Outpatient Memory Clinic Working Group (2010) The new Alzheimer's criteria in a naturalistic series of patients with mild cognitive impairment. J Neurol 257, 2004-2014.
Foster NL (2007) A new framework for the diagnosis of Alzheimer's disease. Lancet Neurol 6, 667-669.
Antonell A, Fortea J, Rami L, Bosch B, Balasa M, Sánchez-Valle R, Iranzo A, Molinuevo JL, Lladó A (2011) Different profiles of Alzheimer's disease cerebrospinal fluid biomarkers in controls and subjects with subjective memory complaints. J Neural Transm 118, 259-262.
Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC (2006) [11C]PIB in nondemented population: Potential antecedent marker of Alzheimer disease. Neurology 67, 446-452.
Hulette CM,Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM (1998) Neuropathological and neuropsychological changes in "normal" aging: Evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol 57, 1168-1174.
Molinuevo JL, Sánchez-Valle R, Lladó A, Fortea J, Bartrés-FazD, Rami L (2011) Identifying earlier Alzheimer's disease: Insights from the preclinical and prodromal phases. Neurodegener Dis 10, 158-160.
Buchhave P, Minthon L, Zetterberg H, Wallin AK, Blennow K, Hansson O (2012) Cerebrospinal fluid levels of-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry 69, 98-106.