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

Article type: Research Article

Authors: Naudé, Petrus J.W.^{a; b; *; 1} | Dekker, Alain D.^{a; c; 1} | Coppus, Antonia M.W.^{d; e; f} | Vermeiren, Yannick^c | Eisel, Ulrich L.M.^{b; g} | van Duijn, Cornelia M.^e | Van Dam, Debby^c | De Deyn, Peter P.^{a; c}

Affiliations: [a] Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands | [b] Department of Molecular Neurobiology, University of Groningen, Groningen, The Netherlands | [c] Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium | [d] Dichterbij, Center for the Intellectually Disabled, Gennep, The Netherlands | [e] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands | [f] Department of Primary and Community Care (152 ELG), Radboud University Medical Center, Nijmegen, The Netherlands | [g] University Center of Psychiatry & Interdisciplinary Center of Psychopathology of Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Correspondence: [*] Correspondence to: Petrus J.W. Naudé, Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. Tel.: +31 50 363 2363; Fax: +31 50 363 2331; E-mail: p.j.w.naude@umcg.nl.

Note: [1] These authors contributed equally to this work.

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, Aβn40, and Aβn42 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 Aβn42 in demented DS individuals and with Aβ40 and Aβn40 in the non-demented DS group. NGAL was negatively associated with Aβ42/Aβ40 and Aβn42/Aβn40 ratios in converted DS subjects. These associations persisted for Aβn40, Aβ42/Aβ40, and Aβn42/Aβn40 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.

Keywords: Alzheimer's disease, amyloid-β, apolipoprotein E, biomarker, down syndrome, inflammation, lipocalin 2, platelets

DOI: 10.3233/JAD-142514

Journal: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 733-743, 2015