Serum NGAL is Associated with Distinct Plasma Amyloid-β Peptides According to the Clinical Diagnosis of Dementia in Down Syndrome

Pieter Naudé, Alain D. Dekker, Antonia M W Coppus, Yannick Vermeiren, Ulrich L. M. Eisel, Cornelia M. van Duijn, Debby Van Dam, Peter P. De Deyn

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Background: The majority of people with Down syndrome (DS) develop dementia due to Alzheimer's disease (AD). Neuropathological features are characterized by an accumulation of amyloid-beta (A beta) deposits and the presence of an activated immune response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a newly identified (neuro) inflammatory constituent in AD.

Objective: This study examines NGAL as an inflammatory marker in DS and its associations with plasma A beta peptides according to the follow-up clinical diagnosis of dementia.

Methods: Baseline serum NGAL and plasma A beta(40), A beta(42), A beta(n40), and A beta(n42) were quantified in 204 people with DS. The diagnosis of dementia in DS was established by follow-up clinical assessments. The following study groups were characterized: DS with AD at baseline (n = 67), DS without AD (n = 53), and non-demented DS individuals that converted to AD (n = 84). Serum NGAL was analyzed in 55 elderly non-DS, non-demented people.

Results: Serum NGAL levels were significantly increased in DS subjects compared to non-DS people. Serum NGAL levels were not associated with clinical dementia symptoms in DS. However, NGAL was positively associated with A beta(42) and A beta(n42) in demented DS individuals and with A beta(40) and A beta(n40) in the non-demented DS group. NGAL was negatively associated with A beta(42)/A beta(40) and A beta(n42)/A beta(n40) ratios in converted DS subjects. These associations persisted for A beta(n40), A beta(42)/A beta(40), and A beta(n42)/A beta(n40) after adjusting for demographics measures, apolipoprotein E epsilon 4 allele, platelets, and anti-inflammatory medication.

Conclusion: Serum NGAL levels are increased in DS and associated with distinct species of A beta depending on the progression of dementia as diagnosed by baseline and follow-up clinical assessments.

Original languageEnglish
Pages (from-to)733-743
Number of pages11
JournalJournal of Alzheimer’s Disease
Volume45
Issue number3
Early online date22-Jan-2015
DOIs
Publication statusPublished - 2015

Keywords

  • Alzheimer's disease
  • amyloid-beta
  • apolipoprotein E
  • biomarker
  • down syndrome
  • inflammation
  • lipocalin 2
  • platelets
  • GELATINASE-ASSOCIATED LIPOCALIN
  • MILD COGNITIVE IMPAIRMENT
  • LATE-LIFE DEPRESSION
  • ALZHEIMERS-DISEASE
  • NEUTROPHIL GELATINASE
  • INTELLECTUAL DISABILITY
  • PLAQUE-FORMATION
  • UNITED-STATES
  • BRAIN
  • PREVALENCE

Cite this