A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer%26apos;s Disease in Belgium

作者：Somers Charisse; Struyfs Hanne; Goossens Joery; Niemantsverdriet Ellis; Luyckx Jill; De Roeck Naomi; De Roeck Ellen; De Vil Bart; Cras Patrick; Martin Jean Jacques; De Deyn Peter Paul; Bjerke Maria; Engelborghs Sebastiaan

来源：Journal of Alzheimer's Disease, 2016, 54(1): 383-395.

DOI：10.3233/JAD-151097

• Alzheimer's disease
• amyloid
• biomarkers
• cerebrospinal fluid
• dementia
• diagnosis
• mild cognitive impairment
• neuropathology
• tau

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-beta peptide of 42 amino acids (A beta(1-42)), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau(181P)). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: A beta(1-42) < 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 A beta(1-42) concentration was below the cutoff, in combination with T-tau and/or P-tau(181P) 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.

• 出版日期2016