A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in Belgium

Article type: Research Article

Authors: 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^d | Cras, Patrick^{d; e} | Martin, Jean-Jacques^c | De Deyn, Peter-Paul^{a; b; c} | Bjerke, Maria^a | Engelborghs, Sebastiaan^{a; b; *}

Affiliations: [a] Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [b] Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium | [c] Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [d] Laboratory of Neurobiology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [e] Department of Neurology, Antwerp University Hospital, Antwerp, Belgium

Correspondence: [*] Correspondence to: Prof. Dr. Sebastiaan Engelborghs, Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Universiteitsplein 1, BE-2610 Antwerp, Belgium. Tel.: +323 265 23 94; E-mail: [email protected].

Abstract: 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.

Keywords: Alzheimer’s disease, amyloid, biomarkers, cerebrospinal fluid, dementia, diagnosis, mild cognitive impairment, neuropathology, tau

DOI: 10.3233/JAD-151097

Journal: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 383-395, 2016