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Analysis of Combined CSF Biomarkers in AD Diagnosis by Valentina De Riva, Elisabetta Galloni, Michela Marcon, Laura Di Dionisio, Cristina Deluca, Lucia Meligrana, Andrea Bolner, Francesco Perini

Background: The new proposed diagnostic criteria for early diagnosis of Alzheimer’s Disease (AD) underline the
value of cerebrospinal fluid (CSF) biomarkers. The first aim of the study was to determine the diagnostic accuracy
of CSF biomarker Aβ1-42, T-tau, and P-tau in differentiating AD patients in our cohort by means of “pure” biomarkers
and in form of a combined analysis of these biomarkers. The second aim of the study was to determine
the diagnostic accuracy of these markers for predicting incipient AD in patients with mild cognitive impairment
Methods: We studied 102 CSF samples: 33 AD [mean age at baseline 71.2 (54 - 86)], 16 MCI [mean age at baseline
71.3 (57 - 78)], 24 non AD dementia, including 7 vascular dementia, 4 frontotemporal degeneration, 5 dementia
with Lewy Body, and 8 with other dementia [mean age at baseline 72.7 (51 - 87)] and 32 non-demented neurological
patients [mean age at baseline 71.3 (45 - 87) referred to as control (CO) later in the text]. A double sandwich
ELISA (Innotest beta amyloid Aβ1-42, hTau and P-tau181 by Innogenetics, Gent, Belgium) was performed to quantify
the concentration of the above biomarkers. The three biomarkers were then combined in the IATI index
[(measured Ab1-42)/(240 + 1.18 *measured tau)], and in the ratios Aβ1-42/T-tau, Aβ1-42/P-tau, T-tau/Aβ1-42 and
Results: Aβ1-42, T-tau and P-tau181 concentration showed statistically significant differences between AD and CO
(327.2 pg/mL ± 150.2 pg/mL and 659.4 pg/mL ± 254.2 pg/mL; 508.2 pg/mL ± 360.2 pg/mL and 305.3 pg/mL ±
228.9 pg/mL; 82.2 pg/mL ± 26.1 pg/mL and 45.3 pg/mL ± 26.4 pg/mL, respectively, p < 0.05), while the difference
between AD and MCI was statistically different only for Aβ1-42 (327.2 pg/mL ± 150.2 pg/mL and 600.8 ±
271.9 pg/mL, respectively, p < 0.05). The IATI index was 0.5 ± 0.3 in AD, 0.9 ± 0.6 in MCI, 1.37 ± 0.9 in non AD
dementia and 1.26 ± 0.8 in non-demented neurological patients. With a cut-off fixed at 1 the sensitivity and specificity
of the IATI index in discriminating AD from CO was 84% and 52%, respectively.
Conclusions: This study confirms the great significance of CSF biomarker measurements in AD diagnosis in clinical
routine. It is understood that a clinical diagnostic work-up is necessary in the process. Moreover, a biochemical
profile of CSF biomarkers requires further investigations.

DOI: 10.7754/Clin.Lab.2013.130440