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Lipocalin 2: novel inflammatory actor in Alzheimer's disease
Author(s) -
Eisel Ulrich,
Dekens Doortje,
DeDeyn Peter,
Naudé Pieter
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.835.2
Subject(s) - lipocalin , neuroprotection , pathogenesis , disease , biomarker , medicine , dementia , neuroinflammation , neuroscience , bioinformatics , immunology , biology , genetics
Inflammatory processes are of particular importance in Alzheimer's disease (AD). We identified Lipocalin 2 as a neuroinflammatory component that is increased during early stages of the disease and can play an important role in the pathogenesis of AD. Lipocalin 2 in the brain is a result of Tumor Necrosis Factor alpha (TNF‐α) signaling and high levels of Lipocalin 2 expression are found in brain regions with AD pathology. Contrary to other inflammatory proteins, Lipocalin 2 levels are strongly decreased in the cerebrospinal fluid (CSF) of Mild Cognitive Impaired (MCI) patients and AD patients, as compared to healthy subjects. In a large clinical cohort we found that Lipocalin 2 significantly increased in depressed elderly females with cognitive impairments, a population group at high risk to develop Alzheimer's disease. We also found that Lipocalin 2 is associated with distinct amyloid beta species related to the progression of dementia in Downs Syndrome. Mechanistically, Lipocalin 2 sensitizes neurons to the toxic effects of oligomeric forms of Aβ and silences the neuroprotective mechanisms by inhibiting TNF‐α mediated signaling via its receptor 2. The present study introduces Lipocalin 2 as a novel neuro‐immunopathogen in early clinical stages of AD. The clinical data suggest Lipocalin 2 as potential biomarker for early forms of AD, since dynamic alterations in expression of the protein appear to parallel disease progression. In addition, Lipocalin 2 may function as a (neuro)inflammatory marker linking late‐life depression and AD.