Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer's disease patients: A CSF and FDG PET study

Aims: Physiopathological mechanisms of Alzheimer's disease (AD) are still matter of debate. Especially the role of amyloid beta and tau pathology in the development of the disease are still matter of debate. Changes in tau and amyloid beta peptide concentration in cerebrospinal fluid (CSF) and hypometabolic patterns at fluorine-18 fluorodeoxyglucose (F-18-FDG) PET scanning are considered as biomarkers of AD. The present study was aimed to evaluate the relationships between the concentrations of CSF total Tau (t-Tau), phosphorilated Tau (p-Tau) and A beta(1-42) amyloid peptide with F-18-FDG brain distribution in a group of patients with AD. Materials and methods: We examined 131 newly diagnosed AD patients according to the NINCDS-ADRDA criteria and 20 healthy controls. The mean (+/- SD) age of the patients was 70 (+/- 7) years; 57 were male and 74 were female. All patients and controls underwent a complete clinical investigation, including medical history, neurological examination, mini-mental state examination (MMSE), a complete blood screening (including routine exams, thyroid hormones and a complete neuropsychological evaluation). Structural MRI was performed not earlier than 1 month before the F-18-FDG PET/CT. The following patients were excluded: those with isolated deficits and/or unmodified MMSE (= 25/30) on revisit (period of follow-up: 6, 12 and 18 months); patients who had had a clinically manifest acute stroke in the last 6 months with a Hachinsky score greater than 4; and patients with radiological evidence of subcortical lesions. All AD patients were taken off cholinesterase inhibitor treatment throughout the study. We performed lumbar puncture and CSF sampling for diagnostic purposes 2 weeks (+/- 2 days) before the PET/CT scan. The relationship between brain F-FDG uptake and CSF biomarkers was analysed using statistical para-metric mapping (SPM8; Wellcome Department of Cognitive Neurology, London, UK) implemented in Matlab R2012b using the MMSE score, sex and age, and other CSF biomarkers as covariates. Results: t-Tau, p-Tau and A beta(1-42) in CSF resulted 774 +/- 345 pg/ml, 98 +/- 64 pg/ml and 348.8 +/- 111 pg/ml respectively. SPM analysis showed a significant negative correlation between CSF t-Tau and F-18 FDG uptake in right temporal, parietal and frontal lobe (Brodmann areas, BA, 20, 40 and 8; P fdr and few co rr < 0.001, ke 19534). We did not find any significant relationships with other CSF biomarkers. Conclusions: t-Tau deposition in brain is related to temporal, parietal and frontal hypometabolism in AD. (C) 2017 Elsevier B.V. All rights reserved.