Damage to the Locus Coeruleus in Alzheimer's Disease: Potential Causes and Therapeutic Targets

摘要: Therapeutic options for Alzheimer's disease (AD) are limited, and this dearth of treatments necessitates the development of novel therapeutic targets. One such target is the noradrenergic locus coeruleus (LC), a small nucleus located in the brainstem pons. The LC undergoes severe degeneration in AD, however the reasons for this are currently unknown. To address this question, the present dissertation is divided into three parts. In the first, I depleted brain derived neurotrophic factor (BDNF) from the hippocampus (HC) of 5xFAD AD model mice. The resulting decline in LC projections throughout LC target regions, as well as reductions in biosynthetic enzymes for noradrenaline synthesis, indicate that BDNF in the HC is important in maintaining LC function in the AD context. In the second part I tested the LC-targeting drug vindeburnol in 5xFAD mice, known to increase noradrenaline output from LC neurons …