Serum NGAL is Associated with Distinct Plasma Amyloid-β 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-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.

Objective:

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.

Methods:

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.

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 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.

Conclusion:

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.