Agostino Chiaravalloti1, Gaetano Barbagallo2, Maria Ricci3, Alessandro Martorana4, Francesco Ursini5, Pasqualina Sannino6, Georgios Karalis7, Orazio Schillaci8. 1. Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy. Electronic address: agostino.chiaravalloti@uniroma2.it. 2. Institute of Neurology, University Magna Graecia of Catanzaro, Italy. 3. Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy. 4. Department of Neurosciences, University Tor Vergata, Rome, Italy; IRCCS Santa Lucia, Rome, Italy. 5. Department of Health Sciences, University Magna Graecia, Catanzaro, Italy. 6. IRCCS Neuromed, Pozzilli, Italy. 7. Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy. 8. Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
Abstract
AIMS: Physiopathological mechanisms of Alzheimer's disease (AD) are still matter of debate. Especially the role of amyloid β and tau pathology in the development of the disease are still matter of debate. Changes in tau and amyloid β peptide concentration in cerebrospinal fluid (CSF) and hypometabolic patterns at fluorine-18 fluorodeoxyglucose (18F-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 Aβ1-42 amyloid peptide with 18F-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 18F-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 parametric 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 Aβ(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 18F FDG uptake in right temporal, parietal and frontal lobe (Brodmann areas, BA, 20, 40 and 8; P fdr and few corr < 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.
AIMS: Physiopathological mechanisms of Alzheimer's disease (AD) are still matter of debate. Especially the role of amyloid β and tau pathology in the development of the disease are still matter of debate. Changes in tau and amyloid β peptide concentration in cerebrospinal fluid (CSF) and hypometabolic patterns at fluorine-18 fluorodeoxyglucose (18F-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 Aβ1-42 amyloid peptide with 18F-FDG brain distribution in a group of patients with AD. MATERIALS AND METHODS: We examined 131 newly diagnosed ADpatients 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 18F-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 ADpatients 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 parametric 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 Aβ(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 18F FDG uptake in right temporal, parietal and frontal lobe (Brodmann areas, BA, 20, 40 and 8; P fdr and few corr < 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.
Authors: Michael Schöll; Anne Maass; Niklas Mattsson; Nicholas J Ashton; Kaj Blennow; Henrik Zetterberg; William Jagust Journal: Mol Cell Neurosci Date: 2018-12-07 Impact factor: 4.314