Serum and cerebrospinal fluid Neutrophil gelatinase-associated lipocalin (NGAL) levels as biomarkers for the conversion from mild cognitive impairment to Alzheimer's disease dementia

Petrus J.W Naudé,Inez H.G.B Ramakers,Wiesje M Van Der Flier,Lize C Jiskoot,Fransje E Reesink,Jurgen A.H.R Claassen,Huiberdina L Koek,Ulrich L.M Eisel,Peter P De Deyn

doi:10.1016/j.neurobiolaging.2021.07.001

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is an acute phase protein that has been reported as a potential marker for pre-dementia stages of Alzheimer's disease (AD). Longitudinal studies for its association with the conversion of mild cognitive impairment to AD is still lacking. This study included n = 268 study participants with subjective cognitive decline (SCD) (n=82), mild cognitive impairment (MCI) (n=98) and AD dementia (n=88) at baseline and two-year follow-up clinical assessments. Serum and cerebrospinal fluid (CSF)NGAL, CSF amyloid beta1-42, total-Tau, and phospho-Tau levels were measured with ELISA analysis. CSF NGAL levels were significantly lower in MCI participants compared to people with SCD at baseline. Lower baseline CSF NGAL levels predicted MCI converters to AD dementia vs. non-converters after 2-years follow-up. A positive correlation between CSF NGAL and amyloid beta1-42 was found particularly in MCI participants at baseline. NGAL in CSF holds potential to be used as a predictive marker for the conversion of MCI to AD dementia and may reflect pathophysiological processes of prodromal AD neuropathology.

Highlights

A chronic inflammatory response, in addition to amyloid beta (Aβ) and Tau, is considered a core feature in the neuropatho-physiology of Alzheimer’s disease (AD) (Akiyama et al, 2000; Kinney et al, 2018; Krstic and Knuesel, 2013)
People with subjective cognitive decline (SCD) had a higher education compared to the mild cognitive impairment (MCI) and AD dementia study groups (X2 = 6.07, df = 2, p < 0.05)
A total of 59 SCD participants had 2-year follow-up measures of which, 10 participants converted to MCI and 2 participants converted to AD

Summary

Introduction

A chronic inflammatory response, in addition to amyloid beta (Aβ) and Tau, is considered a core feature in the neuropatho-physiology of Alzheimer’s disease (AD) (Akiyama et al, 2000; Kinney et al, 2018; Krstic and Knuesel, 2013). Numerous studies on the associations of peripheral and cerebrospinal fluid (CSF) immune markers of AD have been conducted to identify potential biomarkers and gain insights into the multifaceted neuroimmune mechanisms of early AD. Peripheral and CSF inflammatory makers that reflect the pathophysiological processes of AD pathology have the potential to improve early diagnosis and facilitate monitoring of treatment strategies (Molinuevo et al, 2018)

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