Title | Clinic-Based Validation of Cerebrospinal Fluid Biomarkers with Florbetapir PET for Diagnosis of Dementia. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Álvarez, I, Aguilar, M, González, JManuel, Ysamat, M, Lorenzo-Bosquet, C, Alonso, A, Tartari, JPablo, Romero, S, Diez-Fairen, M, Carcel, M, Pujalte, F, Pastor, P |
Journal | J Alzheimers Dis |
Volume | 61 |
Issue | 1 |
Pagination | 135-143 |
Date Published | 2018 |
ISSN | 1875-8908 |
Keywords | Aged, Amyloid beta-Peptides, Analysis of Variance, Aniline Compounds, Apolipoproteins E, Biomarkers, Cognition Disorders, Dementia, Ethylene Glycols, Female, Humans, Male, Middle Aged, Peptide Fragments, Positron-Emission Tomography, tau Proteins |
Abstract | BACKGROUND: Cerebrospinal fluid (CSF) biomarker studies have shown variable accuracy for diagnosis of Alzheimer's disease (AD); therefore, internal validation is recommended. OBJECTIVE: To investigate the correlation between CSF biomarkers and cerebral 18-Florbetapir positron emission tomography (Amyloid-PET) and calculate their sensitivity and specificity to obtain the optimal clinical cut-off points to diagnose the etiology of cognitive impairment. METHODS: We performed Amyloid-PET scans and CSF biomarker levels analyses in 68 subjects (50 with mild cognitive impairment, 11 with AD dementia, and 7 with non-AD dementia). Visual examination of Amyloid-PET scans was performed. CSF analyses were performed using standard sandwich ELISA. RESULTS: Amyloid-PET was positive in 36 subjects, negative in 26, and inconclusive in 6. Optimal clinical cut-off points for CSF markers were the following: amyloid-β 1-42 (Aβ42) = 629 pg/ml, total tau (t-tau) = 532 pg/ml, phosphorylated tau (p-tau) = 88 pg/ml, and t-tau/Aβ42 ratio = 0.58. T-tau/Aβ42 ratio showed the best sensitivity and specificity (92 and 84%, respectively). T-tau and p-tau CSF levels (r2 = 0.867) followed by the t-tau and t-tau/Aβ42 CSF ratio (r2 = 0.666) showed the strongest inter-marker correlation. Interestingly, subjects with inconclusive Amyloid-PET showed intermediate values for all CSF markers between negative and positive Amyloid-PET groups. CONCLUSIONS: CSF t-tau/Aβ42 ratio appears to be the most accurate AD CSF marker. The presence of intermediate values for CSF markers among the subjects with inconclusive Amyloid-PET suggests the presence of other dementias associated with AD pathology or intermediate phenotypes. |
DOI | 10.3233/JAD-170753 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 29154286 |