Microstructural changes in locus coeruleus-cortical projections in aged bonnet macaques are independent of myelin loss.

The locus coeruleus (LC) is a brainstem nucleus best known for being the primary site of noradrenaline production for the forebrain and is involved in the modulation and optimization of behavioral performance. The LC has many targets throughout the cortex, and ascending projections from the LC join the central tegmental tract (CTT), a well-defined white matter brainstem tract in the pons that terminates in the thalamus. Evidence indicates that the LC is one of the first brain regions to show pathological burden in Alzheimer's disease (AD), and AD patients exhibit structural alterations in the LC and its ascending projections. The extent to which changes occur in the LC and its projections in normal aging, however, is less clear. Analysis of LC-forebrain tractography has historically been difficult due to the small size of the LC as well as the abundance of crossing fibers in the brainstem. Ex vivo magnetic resonance imaging (MRI) allows us to overcome some of these setbacks, as longer scan times can be used to generate higher resolution images than is possible in live subjects. Here, we utilize a cohort of bonnet macaques, an excellent model of normative aging, and analyze the microstructure of the LC and its projections that join the CTT with respect to age. We have been able to overcome issues associated with LC tractography and have found a negative association with age and diffusivity.