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Elevated sulfides are associated with cognitive dysfunction and brain atrophy in Alzheimer's disease and related dementias

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  1. Louisiana State University Health Shreveport

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Published 02 Feb. 2023 | License Creative Commons CC0 1.0 Public Domain Dedication


Description

Emerging evidence indicates that vascular stress is an important contributor to the pathophysiology of Alzheimer's disease and related dementias (ADRD). Hydrogen sulfide (H2S) and its metabolites (acid-labile (e.g., iron-sulfur clusters) and bound (e.g., per-, poly-sulfides)) have been shown to regulate both vascular and neuronal homeostasis. We recently reported that elevated plasma sulfides were associated with cognitive dysfunction and microvascular disease in ADRD; here we extend our previous work to show associations between elevated sulfides and magnetic resonance-based metrics of brain atrophy and white matter integrity. Elevated bound sulfides were associated with decreased measures of gray matter volume, while increased acid labile sulfides were associated with measures of decreased white matter integrity and increased ventricular volume. These findings are consistent with a 'toxic' sulfide model of ADRD. Our results are consistent with a compensatory sulfide response to oxidative stress.

Keywords

| Alzheimer's Disease | hydrogen sulfide | dementia | cortical thickness | white matter integrity | neuroimaging |

References

  • Reekes, T. H., Ledbetter, C. R., Pardue, S., Alexander, J. S., Stokes, K. Y., Bhuiyan, M. A. N., Patterson, J. C., Lofton, K. T., Kevil, C. G., & Disbrow, E. A. (2023). Elevated sulfides are associated with cognitive dysfunction and brain atrophy in alzheimer's disease and related dementias. Submitted to Redox Biology.

Funding

  • NIH 3P2012130701A1S1
  • NIH HL149264-01A1

Citation

Reekes TH, Ledbetter CR, Pardue S, Alexander JS, Stokes KY, Bhuiyan MAN, Patterson JC, Lofton KT, Kevil CG, Disbrow EA (2023) Elevated sulfides are associated with cognitive dysfunction and brain atrophy in Alzheimer's disease and related dementias. G-Node. https://doi.org/10.12751/g-node.l4e76c