Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy
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This study aims to investigate the influence of human immunodeficiency virus (HIV) infection on the neurodegenerative processes normally associated with ageing. We have looked for evidence of beta amyloid and hyperphosphorylated Tau deposition in HIV-infected subjects before and after the advent of highly active anti-retroviral therapy (HAART). In addition we have looked for evidence of axonal damage. We have compared these HIV-positive cases with age-matched controls and with older non-demented controls. We find no evidence of significant premature beta amyloid deposition in HIV-infected cases; however, we do observe elevated levels of hyperphosphorylated Tau in the hippocampus of many HIV-infected subjects, compared with age-matched controls. The greatest levels of hyperphosphorylated Tau are noted in HAART-treated subjects. Axonal damage marked by expression of beta amyloid pre-cursor protein (BAPP) was highly variable in all groups including control subjects. We surmise that HIV infection and/or the use of anti-retroviral therapy may predispose to accelerated neuroageing in the form of hyperphosphorylated Tau deposition in the hippocampus. Within the age groups studied these significant neuropathological changes remained subclinical and were not yet associated with cognitive impairment.
KeywordsHIV HAART Neurodegeneration Hyperphosphorylated Tau Brain
This work was supported by NIH grants R01-13840, R01-13127, SHERT grant F6/05 and MRC grant 9708080. We would like to thank Mr. Alan Wilson for his help in retrieving archived case information.
- 4.Bell JE (1998) The neuropathology of adult HIV infection. Rev Neurol (Paris) 154:816–829Google Scholar
- 6.Boven LA (2000) Macrophages and HIV-1-associated dementia. Arch Immunol Ther Exp (Warsz) 48:273–279Google Scholar
- 17.D’Souza I, Poorkaj P, Hong M, Nochlin D, Lee VM, Bird TD, Schellenberg GD (1999) Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc Natl Acad Sci USA 96:5598–5603CrossRefPubMedGoogle Scholar
- 19.Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L’Heureux D, Regulier EG, Richardson MW, Amini S, Morgello S, Khalili K, Rappaport J (2001) CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 7:528–541CrossRefPubMedGoogle Scholar
- 43.Tozzi V, Balestra P, Galgani S, Narciso P, Ferri F, Sebastiani G, D’Amato C, Affricano C, Pigorini F, Pau FM, De Felici A, Benedetto A (1999) Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment. AIDS 13:1889–1897CrossRefPubMedGoogle Scholar