Multiple Neurodegenerative Pathologies in an Alzheimer's Disease Patient Treated with Fornical Deep Brain Stimulation

Bartholomew White, Constantine G. Lyketsos, Paul B. Rosenberg, Esther S. Oh, Liam Chen

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1383-1387
Number of pages5
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - Apr 20 2021

Bibliographical note

Funding Information:
This work is supported by grant P50AG005146 to the Johns Hopkins Alzheimer's Disease Research Center. Functional Neuromodulation Ltd. sponsored the ADvance study of DBS-f in mild Alzheimer's dementia.

Publisher Copyright:
© 2021 - IOS Press. All rights reserved.


  • Alpha-synuclein
  • Alzheimer's disease
  • Lewy body disease
  • TDP-43
  • amyloid-β
  • deep brain stimulation
  • tau

PubMed: MeSH publication types

  • Case Reports
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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