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

Agostino Chiaravalloti, Gaetano Barbagallo, Maria Ricci, Alessandro Martorana, Francesco Ursini, Pasqualina Sannino, Georgios Karalis, Orazio Schillaci

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalBrain Research
Volume1678
DOIs
Publication statusE-pub ahead of print - Oct 21 2017

Fingerprint

Cerebrospinal Fluid Proteins
tau Proteins
Cerebrospinal Fluid
Alzheimer Disease
Fluorodeoxyglucose F18
Brain
Biomarkers
Amyloid
Parietal Lobe
Peptides
Spinal Puncture
Cholinesterase Inhibitors
Neurologic Examination
Frontal Lobe
Temporal Lobe
Neurology
Thyroid Hormones
Stroke
Pathology

Keywords

  • Alzheimer
  • Brain imaging
  • CSF
  • PET
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer's disease patients : A CSF and FDG PET study. / Chiaravalloti, Agostino; Barbagallo, Gaetano; Ricci, Maria; Martorana, Alessandro; Ursini, Francesco; Sannino, Pasqualina; Karalis, Georgios; Schillaci, Orazio.

In: Brain Research, Vol. 1678, 21.10.2017, p. 116-122.

Research output: Contribution to journalArticle

Chiaravalloti, Agostino ; Barbagallo, Gaetano ; Ricci, Maria ; Martorana, Alessandro ; Ursini, Francesco ; Sannino, Pasqualina ; Karalis, Georgios ; Schillaci, Orazio. / Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer's disease patients : A CSF and FDG PET study. In: Brain Research. 2017 ; Vol. 1678. pp. 116-122.
@article{6b5105614e6f481c85a89ef842d2726e,
title = "Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer's disease patients: A CSF and FDG PET study",
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.",
keywords = "Alzheimer, Brain imaging, CSF, PET, Tau",
author = "Agostino Chiaravalloti and Gaetano Barbagallo and Maria Ricci and Alessandro Martorana and Francesco Ursini and Pasqualina Sannino and Georgios Karalis and Orazio Schillaci",
year = "2017",
month = "10",
day = "21",
doi = "10.1016/j.brainres.2017.10.016",
language = "English",
volume = "1678",
pages = "116--122",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer's disease patients

T2 - A CSF and FDG PET study

AU - Chiaravalloti, Agostino

AU - Barbagallo, Gaetano

AU - Ricci, Maria

AU - Martorana, Alessandro

AU - Ursini, Francesco

AU - Sannino, Pasqualina

AU - Karalis, Georgios

AU - Schillaci, Orazio

PY - 2017/10/21

Y1 - 2017/10/21

N2 - 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.

AB - 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.

KW - Alzheimer

KW - Brain imaging

KW - CSF

KW - PET

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=85032200971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032200971&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2017.10.016

DO - 10.1016/j.brainres.2017.10.016

M3 - Article

AN - SCOPUS:85032200971

VL - 1678

SP - 116

EP - 122

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -