Amyloid-β PET-Correlation with cerebrospinal fluid biomarkers and prediction of Alzheimer´s disease diagnosis in a memory clinic.

Ebba Gløersen Müller,Almira Babovic,Nenad Bogdanovic,Trine Holt Edwin,Sigrid Stensby Navelsaker,Mona Elisabeth Revheim,Caroline Stokke,Anne Brita Knapskog,Stephen D Ginsberg

doi:10.1371/journal.pone.0221365

Abstract

BackgroundAlzheimer’s disease (AD) remains a clinical diagnosis but biomarkers from cerebrospinal fluid (CSF) and more lately amyloid imaging with positron emission tomography (PET), are important to support a diagnosis of AD.ObjectiveTo compare amyloid-β (Aβ) PET imaging with biomarkers in CSF and evaluate the prediction of Aβ PET on diagnosis in a memory clinic setting.MethodsWe included 64 patients who had lumbar puncture and Aβ PET with 18F-Flutemetamol performed within 190 days. PET was binary classified (Flut+ or Flut-) and logistic regression analyses for correlation to each CSF biomarker; Aβ 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), were performed. Cut-off values were assessed by receiver operating characteristic (ROC) curves. Logistic regression was performed for prediction of clinical AD diagnosis. We assessed the interrater agreement of PET classification as well as for diagnoses, which were made both with and without knowledge of PET results.ResultsThirty-two of the 34 patients (94%) in the Flut+ group and nine of the 30 patients (30%) in the Flut- group had a clinical AD diagnosis. There were significant differences in all CSF biomarkers in the Flut+ and Flut- groups. Aβ42 showed the highest correlation with 18F-Flutemetamol PET with a cut-off value of 706.5 pg/mL, corresponding to sensitivity of 88% and specificity of 87%. 18F-Flutemetamol PET was the best predictor of a clinical AD diagnosis. We found a very high interrater agreement for both PET classification and diagnosis.ConclusionsThe present study showed an excellent correlation of Aβ42 in CSF and 18F-Flutemetamol PET and the presented cut-off value for Aβ42 yields high sensitivity and specificity for 18F-Flutemetamol PET. 18F-Flutemetamol PET was the best predictor of clinical AD diagnosis.

Highlights

Alzheimers disease (AD) is a progressive degenerative disease of the brain that mainly affect older people
The present study showed an excellent correlation of Aβ 42 (Aβ42) in cerebrospinal fluid (CSF) and 18F-Flutemetamol positron emission tomography (PET) and the presented cut-off value for Aβ42 yields high sensitivity and specificity for 18FFlutemetamol PET. 18F-Flutemetamol PET was the best predictor of clinical Alzheimer’s disease (AD) diagnosis
Evidence shows that decreased levels of amyloid β (Aβ) consisting of 42 amino acids (Aβ42) in CSF or a positive Aβ PET is closely related to Aβ deposition in neuritic plaques [9, 10] while increased levels of phosphorylated tau protein (P-tau) in CSF or a positive tau-PET is closely related to fibrillar tau accumulation in neurofibrillary tangles [11,12,13]

Summary

Methods

We included 64 patients who had lumbar puncture and Aβ PET with 18F-Flutemetamol performed within 190 days. PET was binary classified (Flut+ or Flut-) and logistic regression analyses for correlation to each CSF biomarker; Aβ 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), were performed. Cut-off values were assessed by receiver operating characteristic (ROC) curves. Logistic regression was performed for prediction of clinical AD diagnosis. We assessed the interrater agreement of PET classification as well as for diagnoses, which were made both with and without knowledge of PET results

Results

Conclusions

Introduction

Materials and methods

Discussion