, Volume 15, Issue 2, pp 131-138

Increased frequency of α-synuclein in the substantia nigra in human immunodeficiency virus infection

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Abstract

The frequency of neurodegenerative markers among long surviving human immunodeficiency virus (HIV)-infected individuals is unknown, therefore, the present study investigated the frequency of α-synuclein, β-amyloid, and HIV-associated brain pathology in the brains of older HIV-infected individuals. We examined the substantia nigra of 73 clinically well-characterized HIV-infected individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We also examined the frontal and temporal cortical regions of a subset of 36 individuals. Neuritic α-synuclein expression was found in 16% (12/73) of the substantia nigra of the HIV+cases and none of the older control cases (0/18). β-Amyloid deposits were prevalent and found in nearly all of the HIV+ cases (35/36). Despite these increases of degenerative pathology, HIV-associated brain pathology was present in only 10% of cases. Among older HIV+adults, HIV-associated brain pathology does not appear elevated; however, the frequency of both α-synuclein and β-amyloid is higher than that found in older healthy persons. The increased prevalence of α-synuclein and β-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease.

Drs. N. Khanlou and D. J. Moore are serving as joint first authors.
This work was supported by NIMH Center grant MH62512 and the California NeuroAIDS Tissue Network (CNTN) grants R24 MH59745 and U01 MH083506.
The HIV Neurobehavioral Research Center (HNRC) is supported by Center award MH 62512 from NIMH. The San Diego HIV Neurobehavioral Research Center (HNRC) group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and includes Director: Igor Grant, MD; Co-Directors: J. Hampton Atkinson, MD, Ronald J. Ellis, MD, PhD, and J. Allen McCutchan, MD; Center Manager: Thomas D. Marcotte, PhD; Heather Bentley, CCRA; Melanie Sherman; Naval Hospital San Diego: Braden R. Hale, MD, MPH (P.I.); Neuromedical Component: Ronald J. Ellis, MD, PhD (P.I.), J. Allen McCutchan, MD, Scott Letendre, MD, Edmund Capparelli, PharmD, Rachel Schrier, PhD; Jennifer Marquie-Beck; Terry Alexander, RN; Janis Durelle; Neurobehavioral Component: Robert K. Heaton, PhD (P.I.), Mariana Cherner, PhD, Steven Paul Woods, PsyD, David J. Moore, PhD; Matthew Dawson; Neuroimaging Component: Terry Jernigan, PhD (P.I.), Christine Fennema-Notestine, PhD, Sarah L. Archibald, MA, John Hesselink, MD, Jacopo Annese, PhD, Michael J. Taylor, PhD, Brian Schweinsburg, PhD; Neurobiology Component: Eliezer Masliah, MD (P.I.), Ian Everall, FRCPsych, FRCPath, PhD, Cristian Achim, MD, PhD; Neurovirology Component: Douglas Richman, MD, (P.I.), David M. Smith, MD; International Component: J. Allen McCutchan, MD (P.I.); Developmental Component: Ian Everall, FRCPsych., FRCPath., PhD (P.I.), Stuart Lipton, MD, PhD; Clinical Trials Component: J. Allen McCutchan, MD, J. Hampton Atkinson, MD, Ronald J. Ellis, MD, PhD, Scott Letendre, MD; Participant Accrual and Retention Unit: J. Hampton Atkinson, MD (P.I.), Rodney von Jaeger, MPH; Data Management Unit: Anthony C. Gamst, PhD (P.I.), Clint Cushman (Data Systems Manager), Daniel R. Masys, MD (Senior Consultant); Statistics Unit: Ian Abramson, PhD (P.I.), Florin Vaida, PhD, Christopher Ake, PhD.