The role of lipocalin 2 in Alzheimer's disease and depression

PhD ceremony: Mr. P.J.W. Naudé, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: The role of lipocalin 2 in Alzheimer's disease and depression

Promotor(s): prof. J.A. den Boer, prof. P.G.M. Luiten, prof. U.L.M. Eisel

Faculty: Medical Sciences

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in the elderly, characterized by severe memory impairments. An important goal for today’s research is to identify early processes of AD before the dementia manifests itself. Studies have shown that both increased immune activation and symptoms of depression can pose as significant risk factors for the development of AD. The aim of this research project was to investigate the role of inflammation in AD and depression in the elderly. This investigation was performed by several research disciplines that enabled translation from basic to clinical research.

In this project we identified a novel inflammatory molecule in mouse neuronal cells, called Lipocalin 2. Analyses from human samples show that Lipocalin 2 is increased in the same brain regions that are affected by AD pathology. Abnormal Lipocalin 2 concentrations were also found in cerebrospinal fluid and blood in patients both with early stages of AD and with fully developed AD. Investigations on the responsible molecular mechanisms with cell cultures showed that Lipocalin 2 can promote nerve cell death when they are exposed to the amyloid toxins known in AD. Further clinical investigations revealed that increased Lipocalin 2 levels are significantly associated with symptoms of depression in the elderly. Interestingly, Lipocalin 2 levels are significantly increased in depressed patients with cognitive impairments, which is a high risk factor for AD. The molecular and clinical results from this study point to Lipocalin 2 as promising early diagnostic marker and drug target for AD and late-life depression.