Phosphorylated low-density lipoprotein receptor-related protein 6 is prevalent in hippocampal progenitor cells and circuits of aged human hippocampus

Christopher P. Sullivan, Rosemary Elliott-Bryant, Anish Kanesa-Thasan, Ann C. McKee, Richard E. Fine, John M. Wells, Peter J. Morin

Department of Biochemistry, Boston University School of Medicine, Boston, USA.
Department of Neurology, Boston University School of Medicine, Boston, USA.
Geriatric Research Education and Clinical Center, Bedford VA Hospital, Bedford, USA.

DOI: 10.4236/aad.2013.24017                

Abstract

Wnt signaling has been implicated in Alzheimer’s disease (AD) pathogenesis, but no studies have described Wnt signaling in aging brain. Phosphorylation of the Wnt coreceptor, low-density lipoprotein receptor-related protein 6 (Lrp6), is a sensitive indicator of Wnt ligand-receptor interaction and canonical Wnt signaling. We report that in aged human temporal lobe, the phospho-Lrp6 (pLrp6) epitope localizes to neurons in the entorhinal cortex (EC), the dentate gyrus (DG), and the hippocampal formation, especially in the CA3 field. Activated Lrp6 is detected in neuronal soma and in neuronal processes, particularly in the mossy fiber terminals in the stratum lucidum of CA3. These three regions and their connectivity represent the afferent arm of the major hippocampal circuit. In the DG, cells positive for pLrp6 include Type 1 and Type 2 hippocampal progenitor cells. Overall, these data indicate regional Wnt receptor activation in the human hippocampus that is most prominent in the cells comprising the afferent arm of the major hippocampal circuit that is associated with learning and memory functions. These findings are consistent with data from rodent studies which suggest an important role for Wnts in adult neurogenesis in the human DG. We speculate that Wnt signaling may be an activity-dependent trophic influence in the hippocampus.

Keywords

Wnt; LRP6; Hippocampus; CA3; Neurogenesis; Alzheimer’s

Conflicts of Interest

The authors declare no conflicts of interest.

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