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

Abstract

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-β (Aβ) deposits and the presence of an activated immune response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a newly identified (neuro)inflammatory constituent in AD. This study examines NGAL as an inflammatory marker in DS and its associations with plasma Aβ peptides according to the follow-up clinical diagnosis of dementia. Baseline serum NGAL and plasma Aβ40, Aβ42, Aβ(n40), and Aβ(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. 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 Aβ42 and Aβ(n42) in demented DS individuals and with Aβ40 and Aβ(n40) in the non-demented DS group. NGAL was negatively associated with Aβ42/Aβ40 and Aβ(n42)/Aβ(n40) ratios in converted DS subjects. These associations persisted for Aβ(n40), Aβ42/Aβ40, and Aβ(n42)/Aβ(n40) after adjusting for demographics measures, apolipoprotein E ε4 allele, platelets, and anti-inflammatory medication. Serum NGAL levels are increased in DS and associated with distinct species of Aβ depending on the progression of dementia as diagnosed by baseline and follow-up clinical assessments.