Lipocalin 2 and the pathophysiology of Alzheimer's disease

Alzheimer’s disease (AD) is a devastating brain disease, causing progressive cognitive problems and behavioral changes. No therapies are available yet to efficiently slow down, prevent or cure this disease. This clearly indicates that our understanding of the pathophysiology of AD is still incomplete. However, it is becoming increasingly clear that chronic inflammation in the brain (termed ‘neuroinflammation’) plays an essential role in the development and progression of AD. As such, the cellular and molecular mechanisms involved in chronic neuroinflammation are being studied intensively, with the aim to obtain a better understanding of the pathophysiology of AD and to find efficient treatments for AD. Our group previously identified Lipocalin 2 (Lcn2) as an inflammatory factor that potentially contributes to AD pathology. In this thesis we aimed to gain more insight into the role of Lcn2 in AD. The results show that Lcn2 protein levels are increased in the human AD brain as well as a mouse model of AD. We also report that Lcn2 does not affect major pathological characteristics (such as memory problems) in an AD mouse model, but does contribute to brain iron accumulation and lower body weight. Furthermore, we propose iron chelators as possible inhibitors of AD-related Lcn2 overproduction in the brain, and provide more insight into the potential suitability of Lcn2 (in cerebrospinal fluid) as a biomarker for AD diagnosis. Altogether, the results from this thesis indicate that Lcn2 affects certain pathological processes in AD, and may be a valuable therapeutic target and diagnostic marker for AD.