%0 Journal Article %J J Alzheimers Dis %D 2018 %T Clinic-Based Validation of Cerebrospinal Fluid Biomarkers with Florbetapir PET for Diagnosis of Dementia. %A Álvarez, Ignacio %A Aguilar, Miquel %A González, Jose Manuel %A Ysamat, Montse %A Lorenzo-Bosquet, Carles %A Alonso, Alvaro %A Tartari, Juan Pablo %A Romero, Silvia %A Diez-Fairen, Monica %A Carcel, Maria %A Pujalte, Francisco %A Pastor, Pau %K Aged %K Amyloid beta-Peptides %K Analysis of Variance %K Aniline Compounds %K Apolipoproteins E %K Biomarkers %K Cognition Disorders %K Dementia %K Ethylene Glycols %K Female %K Humans %K Male %K Middle Aged %K Peptide Fragments %K Positron-Emission Tomography %K tau Proteins %X

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.

%B J Alzheimers Dis %V 61 %P 135-143 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29154286?dopt=Abstract %R 10.3233/JAD-170753 %0 Journal Article %J J Alzheimers Dis %D 2016 %T MAPT H1 Haplotype is Associated with Late-Onset Alzheimer's Disease Risk in APOEɛ4 Noncarriers: Results from the Dementia Genetics Spanish Consortium. %A Pastor, Pau %A Moreno, Fermín %A Clarimón, Jordi %A Ruiz, Agustin %A Combarros, Onofre %A Calero, Miguel %A López de Munain, Adolfo %A Bullido, Maria J %A de Pancorbo, Marian M %A Carro, Eva %A Antonell, Anna %A Coto, Eliecer %A Ortega-Cubero, Sara %A Hernandez, Isabel %A Tárraga, Lluís %A Boada, Merce %A Lleo, Alberto %A Dols-Icardo, Oriol %A Kulisevsky, Jaime %A Vázquez-Higuera, José Luis %A Infante, Jon %A Rábano, Alberto %A Fernández-Blázquez, Miguel Ángel %A Valentí, Meritxell %A Indakoetxea, Begoña %A Barandiarán, Myriam %A Gorostidi, Ana %A Frank-García, Ana %A Sastre, Isabel %A Lorenzo, Elena %A Pastor, María A %A Elcoroaristizabal, Xabier %A Lennarz, Martina %A Maier, Wolfang %A Rámirez, Alfredo %A Serrano-Ríos, Manuel %A Lee, Suzee E %A Sánchez-Juan, Pascual %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Apolipoprotein E4 %K Female %K Frontotemporal Dementia %K Genetic Predisposition to Disease %K Haplotypes %K Humans %K Logistic Models %K Male %K Middle Aged %K Polymorphism, Single Nucleotide %K Spain %K tau Proteins %X

The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR) = 2.03; p = 0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0005). Stratification analysis showed that this association was mainly driven by APOE ɛ4 noncarriers (OR = 1.14; p = 0.0025). MAPT H1 was also associated with risk for PD (OR = 1.30; p = 0.0003) and PSP (OR = 3.18; p = 8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ɛ4 AD.

%B J Alzheimers Dis %V 49 %P 343-52 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26444794?dopt=Abstract %R 10.3233/JAD-150555