Affiliations: [a] Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| [b] Current affiliation: Department of Pathology, Emory School of Medicine, Atlanta, GA, USA
| [c] Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
| [d] Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
| [e] Current affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA
Correspondence:
[*]
Correspondence to: Esther S. Oh, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. E-mail: eoh9@jhmi.edu; Liam Chen, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA. E-mail: llchen@umn.edu.
Abstract: As an established treatment for movement disorders, deep brain stimulation (DBS) has been adapted for the treatment of Alzheimer’s disease (AD) by modulating fornix activity. Although it is generally regarded as a safe intervention in patients over 65 years of age, the complex neurophysiology and interconnection within circuits connected to the fornix warrants a careful ongoing evaluation of the true benefit and risk potential of DBS on slowing cognitive decline in AD patients. Here we report on a patient who died long after being implanted with a DBS device who donated her brain for neuropathologic study. The autopsy confirmed multiple proteinopathies including AD-related change, diffuse neocortical Lewy body disease, TDP-43 proteinopathy, and a nonspecific tauopathy. We discuss the possible mechanisms of these overlapping neurodegenerative disorders and caution that future studies of DBS for AD will need to take these findings into consideration.
Keywords: Alpha-synuclein, Alzheimer’s disease, amyloid-β, deep brain stimulation, Lewy body disease, tau, TDP-43
