%0 Journal Article %J J Alzheimers Dis %D 2016 %T A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Belgium. %A Somers, Charisse %A Struyfs, Hanne %A Goossens, Joery %A Niemantsverdriet, Ellis %A Luyckx, Jill %A De Roeck, Naomi %A De Roeck, Ellen %A De Vil, Bart %A Cras, Patrick %A Martin, Jean-Jacques %A De Deyn, Peter-Paul %A Bjerke, Maria %A Engelborghs, Sebastiaan %X

During the past ten years, over 5,000 cerebrospinal fluid (CSF) samples were analyzed at the Reference Center for Biological Markers of Dementia (BIODEM), UAntwerp, for core Alzheimer's disease (AD) CSF biomarkers: amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: Aβ1-42 <638.5 pg/mL, T-tau >296.5 pg/mL, P-tau181P >56.5 pg/mL. A CSF biomarker profile was considered to be suggestive for AD if the CSF Aβ1-42 concentration was below the cutoff, in combination with T-tau and/or P-tau181P values above the cutoff (IWG2 criteria for AD). Biomarker analyses were requested for following clinical indications: 1) neurochemical confirmation of AD in case of clinical AD, 2) neurochemical confirmation of AD in case of doubt between AD and a non-AD dementia, 3) neurochemical diagnosis of prodromal AD in case of mild cognitive impairment, 4) neurochemical confirmation of AD in case of psychiatric symptoms (like depression, psychosis), or 5) other clinical indications. During these ten years, the number of yearly referred samples increased by 238% and clinical indications for referral showed a shift from neurochemical confirmation of AD in case of clinical AD to differential dementia diagnosis in case of doubt between AD and a non-AD dementia. Four percent of the patients also had a postmortem neuropathological examination. Together, these biomarker data were the basis for several research papers, and significantly contributed to the validation of these biomarkers in autopsy-confirmed subjects.

%B J Alzheimers Dis %V 54 %P 383-95 %8 2016 Aug 10 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27567807?dopt=Abstract %R 10.3233/JAD-151097 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Validation of microRNAs in Cerebrospinal Fluid as Biomarkers for Different Forms of Dementia in a Multicenter Study. %A Müller, Mareike %A Kuiperij, H Bea %A Versleijen, Alexandra A M %A Chiasserini, Davide %A Farotti, Lucia %A Baschieri, Francesca %A Parnetti, Lucilla %A Struyfs, Hanne %A De Roeck, Naomi %A Luyckx, Jill %A Engelborghs, Sebastiaan %A Claassen, Jurgen A %A Verbeek, Marcel M %X

MicroRNAs (miRNAs) regulate translational inhibition of proteins, but are also detected in body fluids, including cerebrospinal fluid (CSF), where they may serve as disease-specific biomarkers. Previously, we showed differential expression of miR-146a, miR-29a, and miR-125b in the CSF of Alzheimer's disease (AD) patients versus controls. In this study, we aim to confirm these findings by using larger, independent sample cohorts of AD patients and controls from three different centers. Furthermore, we aim to identify confounding factors that possibly arise using such a multicenter approach. The study was extended by including patients diagnosed with mild cognitive impairment due to AD, frontotemporal dementia and dementia with Lewy bodies. Previous results of decreased miR-146a levels in AD patients compared to controls were confirmed in one center. When samples from all three centers were combined, several confounding factors were identified. After controlling for these factors, we did not identify differences in miRNA levels between the different groups. However, we provide suggestions to circumvent various pitfalls when measuring miRNAs in CSF to improve future studies.

%B J Alzheimers Dis %V 52 %P 1321-33 %8 2016 Apr 16 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27104900?dopt=Abstract %R 10.3233/JAD-160038