title: Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.
abstract: Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE > 20 points, n=30) and moderate (MMSE < 21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [κ]=0.34, p=0.016) for t-tau, 68% (κ=0.10, n.s.) for p-tau181, and 68% (κ=0.04, n.s.) for Aβ1-42. No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, κ=0.77, p=0.001) and p-tau181 (88%, κ=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer's dementia, while this is not the case in subjects at an earlier disease stage.
authors: Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Germany. igor.yakushev@uni-mainz.de
authors: Igor
authors: I
authors: Yakushev
authors: Matthias J
authors: MJ
authors: Muller
authors: Hans-Georg
authors: HG
authors: Buchholz
authors: Ulrike
authors: U
authors: Lang
authors: Heidi
authors: H
authors: Rossmann
authors: Harald
authors: H
authors: Hampel
authors: Mathias
authors: M
authors: Schreckenberger
authors: Andreas
authors: A
authors: Fellgiebel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D019540:Area Under Curve; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18