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

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.