Higher buccal mitochondrial DNA and mitochondrial common deletion number are associated with markers of neurodegeneration and inflammation in cerebrospinal fluid

Dipesh Solanky, Jerel A. Fields, Jennifer E. Iudicello, Ronald J. Ellis, Donald Franklin, David B. Clifford, Benjamin B. Gelman, Christina M. Marra, Susan Morgello, Leah H. Rubin, Igor Grant, Robert K. Heaton, Scott L. Letendre, Sanjay R. Mehta

Research output: Contribution to journalArticlepeer-review

Abstract

Human immunodeficiency virus (HIV) infection is potentially associated with premature aging, but demonstrating this is difficult due to a lack of reliable biomarkers. The mitochondrial (mt) DNA “common deletion” mutation (mtCDM) is a 4977-bp deletion associated with aging and neurodegenerative diseases. We examined how mtDNA and mtCDM correlate with markers of neurodegeneration and inflammation in people with and without HIV (PWH and PWOH). Data from 149 adults were combined from two projects involving PWH (n = 124) and PWOH (n = 25). We measured buccal mtDNA and mtCDM by digital droplet PCR and compared them to disease and demographic characteristics and soluble biomarkers in cerebrospinal fluid (CSF) and blood measured by immunoassay. Participants had a median age of 52 years, with 53% white and 81% men. Median mtDNA level was 1,332 copies/cell (IQR 1,201–1,493) and median mtCDM level was 0.36 copies × 102/cell (IQR 0.31–0.42); both were higher in PWH. In the best model adjusting for HIV status and demographics, higher mtDNA levels were associated with higher CSF amyloid-β 1–42 and 8-hydroxy-2'-deoxyguanosine and higher mtCDM levels were associated with higher plasma soluble tumor necrosis factor receptor II. The differences in mtDNA markers between PWH and PWOH support potential premature aging in PWH. Our findings suggest mtDNA changes in oral tissues may reflect CNS processes, allowing the use of inexpensive and easily accessible buccal biospecimens as a screening tool for CSF inflammation and neurodegeneration. Confirmatory and mechanistic studies on mt genome alterations by HIV and ART may identify interventions to prevent or treat neurodegenerative complications.

Original languageEnglish
Pages (from-to)281-290
Number of pages10
JournalJournal of NeuroVirology
Volume28
Issue number2
DOIs
StatePublished - Apr 2022

Keywords

  • Amyloid
  • HIV
  • Mitochondrial DNA
  • Neurodegeneration
  • Neuroinflammation

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