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 language | English |
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Pages (from-to) | 733-743 |
Number of pages | 11 |
Journal | Journal of Alzheimer’s Disease |
Volume | 45 |
Issue number | 3 |
Early online date | 22-Jan-2015 |
DOIs | |
Publication status | Published - 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