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

Neurobiol Aging. 2021 Nov:107:1-10. doi: 10.1016/j.neurobiolaging.2021.07.001. Epub 2021 Jul 10.


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.

Keywords: Amyloid beta; Converters; Follow-up; Lipocalin 2; Neuroinflammation; Prodromal, Biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aftercare
  • Aged
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Disease Progression
  • Female
  • Humans
  • Lipocalin-2 / blood*
  • Lipocalin-2 / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins