CSF α-synuclein correlates with CSF neurogranin in late-life depression

Purpose/aim of the study: Major depressive disorder (MDD) in late life is linked to increased risk of subsequent dementia, but it is still unclear exactly what pathophysiological mechanisms underpin this link. A potential mechanism related to elevated risk of dementia in MDD is increased levels of alpha-synuclein (alpha-Syn), a protein found in presynaptic neuronal terminals. Materials and methods: In this study, we examined cerebrospinal fluid (CSF) levels of alpha-Syn in conjunction with biomarkers of neurodegeneration (amyloid-beta 42, total and phospho tau) and synaptic dysfunction (neurogranin), and measures of memory ability, in 27 cognitively intact older individuals with MDD and 19 controls. Results: Our results show that CSF alpha-Syn levels did not significantly differ across depressed and control participants, but alpha-Syn was directly associated with neurogranin levels, and indirectly linked to poorer memory ability. Conclusions: All in all, we found that alpha-Syn may be implicated in the association between late life MDD and synaptic dysfunction, although further research is needed to confirm these results.

Automated summary

This study investigated the levels of alpha-Syn in the cerebrospinal fluid of cognitively intact older individuals with late-life MDD, and found a direct association between alpha-Syn and neurogranin levels, as well as an indirect link to poorer memory ability. The results suggest that alpha-Syn may be involved in the association between late-life MDD and synaptic dysfunction.