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

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-ß (Aß) 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 Aß peptides according to the follow-up clinical diagnosis of dementia. METHODS: Baseline serum NGAL and plasma Aß40, Aß42, Aß(n40), and Aß(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 Aß42 and Aß(n42) in demented DS individuals and with Aß40 and Aß(n40) in the non-demented DS group. NGAL was negatively associated with Aß42/Aß40 and Aß(n42)/Aß(n40) ratios in converted DS subjects. These associations persisted for Aß(n40), Aß42/Aß40, and Aß(n42)/Aß(n40) after adjusting for demographics measures, apolipoprotein E ε4 allele, platelets, and anti-inflammatory medication. CONCLUSION: Serum NGAL levels are increased in DS and associated with distinct species of Aß depending on the progression of dementia as diagnosed by baseline and follow-up clinical assessments.