Increased frequency of α-synuclein in the substantia nigra in human immunodeficiency virus infection
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.
Keywordsaging brain pathology cognition HIV substantia nigra
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- Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Orrison B, Chen A, Ellis CE, Paylor R, Lu B, Nussbaum RL (2002). Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alphasynuclein. J Neurosci 22: 8797–8807.PubMedGoogle Scholar
- Everall IP, Heaton RK, Marcotte TD, Ellis RJ, McCutchan JA, Atkinson JH, Grant I, Mallory M, Masliah E (1999). Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center. Brain Pathol 9: 209–217.CrossRefPubMedGoogle Scholar
- Piccinini M, Rinaudo MT, Anselmino A, Buccinna B, Ramondetti C, Dematteis A, Ricotti E, Palmisano L, Mostert M, Tovo PA (2005). The HIV protease inhibitors nelfinavir and saquinavir, but not a variety of HIV reverse transcriptase inhibitors, adversely affect human proteasome function. Antivir Ther 10: 215–223.PubMedGoogle Scholar
- Souza JM, Giasson BI, Chen Q, Lee VM, Ischiropoulos H (2000). Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J Biol Chem 275: 18344–18349.CrossRefPubMedGoogle Scholar
- Woods SP, Rippeth JD, Frol AB, Levy JK, Ryan E, Soukup VM, Hinkin CH, Lazzaretto D, Cherner M, Marcotte TD, Gelman BB, Morgello S, Singer EJ, Grant I, Heaton RK (2004). Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. J Clin Exp Neuropsychol 26: 759–778.CrossRefPubMedGoogle Scholar