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

Abstract

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 α-synuclein (α-Syn), a protein found in presynaptic neuronal terminals.

Materials and methods: In this study, we examined cerebrospinal fluid (CSF) levels of α-Syn in conjunction with biomarkers of neurodegeneration (amyloid-β 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 α-Syn levels did not significantly differ across depressed and control participants, but α-Syn was directly associated with neurogranin levels, and indirectly linked to poorer memory ability.

Conclusions: All in all, we found that α-Syn may be implicated in the association between late life MDD and synaptic dysfunction, although further research is needed to confirm these results.

Keywords:

• α-synuclein
• late-life major depressive disorder
• neurogranin
• memory

Acknowledgments

HZ is a Wallenberg Academy Fellow. Parts of this study were presented by the lead author at the Alzheimer’s Association International Conference in London, July 2017.

Disclosure statement

HZ and KB are co-founders of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. KB has served as a consultant or at advisory boards for Alzheon, Axon Neuroscience, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Pfizer, and Roche Diagnostics. HZ has served at scientific advisory boards for Samumed, Wave, CogRx and Roche Diagnostics, and has given lectures in symposia sponsored by Alzecure and Biogen.

No other conflicts of interests are disclosed.

Additional information

Funding

This research was supported by an NIMH (National Institute of Mental Health) grant to NP (R01 MH-080405), Swedish Research Council grants to HZ (2018-02532) and KB (2012-2288), the Swedish Brain Foundation, the Swedish Alzheimer Foundation, and Torsten Söderberg Foundation at the Royal Swedish Academy of Sciences.