Neurodegeneration and Ageing in the HAART Era

  • Bruce J. Brew
  • S. M. Crowe
  • A. Landay
  • Lucette A. Cysique
  • Gilles Guillemin
Invited Review

Abstract

Cognitive impairment and neurodegeneration still occur despite highly active antiretroviral therapy (HAART). While there are many potential reasons for this, there is increasing evidence that such impairment occurs in the absence of a clear cause. Furthermore, there are data that some neurodegenerative diseases, especially Alzheimer’s or an Alzheimer-like illness, are becoming more common in the context of HAART-treated human immunodeficiency virus (HIV) disease. This review will critically examine the evidence underpinning these observations. Potential mechanisms will be discussed with particular emphasis on the effect of ageing and how it overlaps with the effects of HIV disease itself thereby leading to neurodegeneration. The nature of this overlap will then be explored for its potential role in the facilitated expression and development of neurodegenerative diseases. Lastly, there will be a brief discussion of interventions to minimize such neurodegeneration including optimization of HAART for brain entry.

Keywords

HIV HAART neurodegenerative diseases dementia Alzheimer’s 

References

  1. Adle-Biassette H, Chretien F, Wingertsmann L, Hery C, Ereau T, Scaravilli F, Tardieu M, Gray F (1999) Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage. Neuropathol Appl Neurobiol 25:123–133 doi:10.1046/j.1365-2990.1999.00167.x PubMedGoogle Scholar
  2. Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS (2008a) Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS ONE 3(8):2906Google Scholar
  3. Alirezaei M, Kiosses WB, Fox HS (2008b) Decreased neuronal autophagy in HIV dementia: a mechanism of indirect neurotoxicity. Autophagy 4(7):963–966PubMedGoogle Scholar
  4. An SF, Giometto B, Groves M, Miller RF, Beckett AA, Gray F, Tavolato B, Scaravilli F (1997) Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS. J Neuropathol Exp Neurol 56:1262–1268PubMedGoogle Scholar
  5. Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, Zaman T, Stone D, Mefford M, Morgello S, Singer EJ, Wolinsky SM, Gabuzda D (2008) Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One 3:e2516 doi:10.1371/journal.pone.0002516 PubMedGoogle Scholar
  6. Andreasen N, Sjögren M, Blennow K (2003) CSF markers for Alzheimer’s disease: total tau, phospho-tau and Aβ42. World J Biol Psychiatry 4:147–155 doi:10.1080/15622970310029912 PubMedGoogle Scholar
  7. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2006) 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. Acta Neuropathol 111:529–538 doi:10.1007/s00401-006-0037-0 PubMedGoogle Scholar
  8. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799 doi:10.1212/01.WNL.0000287431.88658.8b PubMedGoogle Scholar
  9. Apcher GS, Heink S, Zantopf D, Kloetzel PM, Schmid HP, Mayer RJ, Kruger E (2003) Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal alpha and beta subunits. FEBS Lett 553:200–204 doi:10.1016/S0014-5793(03)01025-1 PubMedGoogle Scholar
  10. Arnsten AF, Cai JX, Steere JC, Goldman-Rakic PS (1995) Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys. J Neurosci 15:3429–3439PubMedGoogle Scholar
  11. Banks WA (1999) Physiology and pathology of the blood–brain barrier: implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. J Neurovirol 5(6):538–555 doi:10.3109/13550289909021284 PubMedGoogle Scholar
  12. Berger JR, Arendt G (2000) HIV dementia: the role of the basal ganglia and dopaminergic systems. J Psychopharmacol 14(3):214–221PubMedCrossRefGoogle Scholar
  13. Berger JR, Kumar M, Kumar A, Fernandez JB, Levin B (1994) Cerebrospinal fluid dopamine in HIV-1 infection. AIDS 8(1):67–71 doi:10.1097/00002030-199401000-00010 PubMedGoogle Scholar
  14. Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C, Phillips A, Porter K (2008) Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Ann Neurol 63:213–221 doi:10.1002/ana.21225 PubMedGoogle Scholar
  15. Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, Raibon E, Lee RV, Benn CL, Soulet D, Magnusson A, Woodman B, Landles C, Pouladi MA, Hayden MR, Khalili-Shirazi A, Lowdell MW, Brundin P, Bates GP, Leavitt BR, Möller T, Tabrizi SJ (2008) A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J Exp Med 205(8):1869–1877PubMedGoogle Scholar
  16. Blalock EM, Chen KC, Stromberg AJ, Norris CM, Kadish I, Kraner SD, Porter NM, Landfield PW (2005) Harnessing the power of gene microarrays for the study of brain aging and Alzheimer’s disease: statistical reliability and functional correlation. Ageing Res Rev 4:481–512PubMedGoogle Scholar
  17. Bowman GL, Kaye JA, Moore M, Waichunas D, Carlson NE, Quinn JF (2007) Blood–brain barrier impairment in Alzheimer disease: stability and functional significance. Neurology 68(21):1809–1814 doi:10.1212/01.wnl.0000262031.18018.1a PubMedGoogle Scholar
  18. Brew BJ (2001) AIDS dementia complex, in HIV neurology. Oxford University Press, OxfordGoogle Scholar
  19. Brew BJ (2004) Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS 18(Suppl 1):S75–S78PubMedGoogle Scholar
  20. Brew BJ, Rosenblum M, Cronin K, Price RW (1995) The AIDS dementia complex and human immunodeficiency virus type 1 brain infection: clinical–virological correlations. Ann Neurol 38:563–570 doi:10.1002/ana.410380404 PubMedGoogle Scholar
  21. Brew BJ, Pemberton L, Blennow K, Wallin A, Hagberg L (2005) CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology 65:1490–1492 doi:10.1212/01.wnl.0000183293.95787.b7 PubMedGoogle Scholar
  22. Brew BJ, Halman M, Catalan J, Sacktor N, Price RW, Brown S, Atkinson H, Clifford DB, Simpson D, Torres G, Hall C, Power C, Marder K, Mc Arthur JC, Symonds W, Romero C (2007) Abacavir in AIDS dementia complex: efficacy and lessons for future trials. PLoS Clin Trials 2(3):e13 doi:10.1371/journal.pctr.0020013 PubMedGoogle Scholar
  23. Brew B, Gisslen M, Pemberton L, Cinque P, Hagberg L, Price R, Blennow K, Zetterberg H, Spudich S CSF t-tau, p-tau and Amyloid-beta 1-42 in HIV Infection (2008) #395 15th Conference on Retroviruses and Opportunistic Infections February 3–6, Boston, MAGoogle Scholar
  24. Buckner CM, Luers AJ, Calderon TM, Eugenin EA, Berman JW (2006) Neuroimmunity and the blood–brain barrier: molecular regulation of leukocyte transmigration and viral entry into the nervous system with a focus on neuroAIDS. J Neuroimmune Pharmacol 1(2):160–181 doi:10.1007/s11481-006-9017-3 PubMedGoogle Scholar
  25. Cherny RA, Legg JT, McLean CA, Fairlie DP, Huang X, Atwood CS, Beyreuther K, Tanzi RE, Masters CL, Bush AI (1999) Aqueous dissolution of Alzheimer’s disease Abeta amyloid deposits by biometal depletion. J Biol Chem 274(33):23223–23228 doi:10.1074/jbc.274.33.23223 PubMedGoogle Scholar
  26. Christensen PM, Gotzsche PC, Brosen K (1998) The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson’s disease: a meta-analysis. Pharmacogenetics 8:473–479 doi:10.1097/00008571-199812000-00003 PubMedGoogle Scholar
  27. Chung KK, Dawson VL, Dawson TM (2001) The role of the ubiquitin–proteasomal pathway in Parkinson’s disease and other neurodegenerative disorders. Trends Neurosci Suppl 11:S7–S14 doi:10.1016/S0166-2236(00)01998-6 Google Scholar
  28. Clarke JN, Lake JA, Burrell CJ, Wesselingh SL, Gorry PR, Li P (2006) Novel pathway of human immunodeficiency virus type 1 uptake and release in astrocytes. Virology 348(1):141–155 doi:10.1016/j.virol.2005.12.004 PubMedGoogle Scholar
  29. Clifford D, Kauwe J, Teshome M, Shah A, Spinner M, Morris J, Holtzman D, Fagan A (2008) Abnormal CSF amyloid beta42 levels link HIV-associated cognitive disease and Alzheimer’s disease. #396b 15th Conference on Retroviruses and Opportunistic Infections February 3–6, Boston, MAGoogle Scholar
  30. Cramer C, Haan MN, Galea S, Langa KM, Kalbfleisch JD (2008) Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 71(5):344–350 doi:10.1212/01.wnl.0000319647.15752.7b PubMedGoogle Scholar
  31. Cuervo AM, Dice JF (1998) How do intracellular proteolytic systems change with age? Front Biosci 3:d25–d43PubMedGoogle Scholar
  32. Cysique LA, Maruff P, Brew BJ (2004a) Prevalence and pattern of neuropsychological impairment in HIV/AIDS infection across pre-HAART and HAART eras: a combined study of 2 cohorts. J Neurovirol 10:350–357 doi:10.1080/13550280490521078 PubMedGoogle Scholar
  33. Cysique L, Maruff P, Brew B (2004b) Antiretroviral therapy in HIV infection: are neurologically active drugs important? Arch Neurol 61:1699–1704 doi:10.1001/archneur.61.11.1699 PubMedGoogle Scholar
  34. Cysique LA, Brew BJ, Halman M, Catalan J, Sacktor N, Price RW, Brown S, Atkinson JH, Clifford DB, Simpson D, Torres G, Hall C, Power C, Marder K, McArthur JC, Symonds W, Romero C (2005) Undetectable cerebrospinal fluid HIV RNA and beta-2 microglobulin do not indicate inactive AIDS dementia complex in highly active antiretroviral therapy-treated patients. J Acquir Immune Defic Syndr 39:426–429 doi:10.1097/01.qai.0000165799.59322.f5 PubMedGoogle Scholar
  35. Cysique LA, Maruff P, Brew BJ (2006a) Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology 66:1447–1450 doi:10.1212/01.wnl.0000210477.63851.d3 PubMedGoogle Scholar
  36. Cysique L, Maruff P, Brew B (2006b) The neuropsychological profile of symptomatic, AIDS and ADC patients in the pre-HAART era: a meta-analysis. J Int Neuropsychol Soc 12:1–15 doi:10.1017/S1355617706060401 Google Scholar
  37. Dore GJ, McDonald A, Li Y, Kaldor J, Brew BJ (2003) Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17(10):1539–1545 doi:10.1097/00002030-200307040-00015 PubMedGoogle Scholar
  38. Esiri MM, Biddolph SC, Morris CS (1998) Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry 65:29–33PubMedGoogle Scholar
  39. Gelman BB, Schuenke K (2004) Brain aging in acquired immunodeficiency syndrome: increased ubiquitin–protein conjugate is correlated with decreased synaptic protein but not amyloid plaque accumulation. J Neurovirol 10:98–108 doi:10.1080/13550280490279816 PubMedGoogle Scholar
  40. Giometto B, An SF, Groves M, Scaravilli T, Geddes JF, Miller R, Tavolato B, Beckett AA, Scaravilli F (1997) Accumulation of beta-amyloid precursor protein in HIV encephalitis: relationship with neuropsychological abnormalities. Ann Neurol 42(1):34–40 doi:10.1002/ana.410420108 PubMedGoogle Scholar
  41. Glisky EL (2007) Changes in cognitive function in human aging. In: Riddle DR (ed) Brain aging: models, methods and mechanisms. CRC, New YorkGoogle Scholar
  42. Goila-Gaur R, Strebel K (2008) HIV-1 Vif, APOBEC, and intrinsic immunity. Retrovirology 5:51PubMedGoogle Scholar
  43. Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL (2005) Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS 19(4):407–411 doi:10.1097/01.aids.0000161770.06158.5c PubMedGoogle Scholar
  44. Guillemin GJ, Brew BJ (2007) Chronic HIV infection leads to an Alzheimer’s disease like illness. Involvement of the kynurenine pathway. Int Congr Ser 1304:324 doi:10.1016/j.ics.2007.07.031 Google Scholar
  45. Guillemin GJ, Smythe GA, Veas LA, Takikawa O, Brew BJ (2003) Abeta 1-42 induces production of quinolinic acid by human macrophages and microglia. Neuroreport 14(18):2311–2315PubMedGoogle Scholar
  46. Guillemin G, Kerr SJ, Brew BJ (2005) Involvement of quinolinic acid in AIDS dementia complex. Neurotox Res 7(1–2):103–124PubMedGoogle Scholar
  47. Guillemin GJ, Cullen K, Smythe G, Kapoor V, Lim E, Garner B, Takikawa O, Brew BJ (2007) Characterization of the kynurenine pathway in human neurons. J Neurosci 27(47):12884–12892 doi:10.1523/JNEUROSCI.4101-07.2007 PubMedGoogle Scholar
  48. Haorah J, Heilman D, Diekmann C, Osna N, Donohue TM Jr, Ghorpade A, Persidsky Y (2004) Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: implications for impaired immune function during disease. Cell Immunol 229(2):139–148 doi:10.1016/j.cellimm.2004.07.005 PubMedGoogle Scholar
  49. Hardy DJ, Hinkin C (2002) Reaction time slowing in adults with HIV: results of a meta-analysis using brinley plots. Brain Cogn 50:25–94 doi:10.1016/S0278-2626(02)00007-6 PubMedGoogle Scholar
  50. Harsher L, Zacks RT, May CP (1999) Inhibitory control, circadian arousal and age. In: Gopher D, Koriat A (eds) Attention and performance XVII. MIT, CambridgeGoogle Scholar
  51. Hartley A (2006) Changing role of the speed of processing construct in the cognitive psychology of human aging. In: Birren JE, Schaie WK (eds) Handbook of the psychology of aging. Elsevier, AmsterdamGoogle Scholar
  52. Haughey NJ, Steiner J, Nath A, McArthur JC, Sacktor N, Pardo C, Bandaru VV (2008) Converging roles for sphingolipids and cell stress in the progression of neuro-AIDS. Front Biosci 1(13):5120–5130 doi:10.2741/3068 Google Scholar
  53. Henry JD, MacLeod MS, Phillips LH, Crawford JR (2004) A meta-analytic review of prospective memory and aging. Psychol Aging 19:27–39 doi:10.1037/0882-7974.19.1.27 PubMedGoogle Scholar
  54. Herber DL, Maloney JL, Roth LM, Freeman MJ, Morgan D, Gordon MN (2006) Diverse microglial responses after intrahippocampal administration of lipopolysaccharide. Glia 53(4):382–391 doi:10.1002/glia.20272 PubMedGoogle Scholar
  55. Heydari AR, Takahashi R, Gutsmann A, You S, Richardson A (1994) Hsp70 and aging. Experientia 50:1092–1098 doi:10.1007/BF01923466 PubMedGoogle Scholar
  56. Heydari AR, You S, Takahashi R, Gutsmann-Conrad A, Sarge KD, Richardson A (2000) Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes. Exp Cell Res 256:83–93 doi:10.1006/excr.2000.4808 PubMedGoogle Scholar
  57. Hinkin CH, Cummings JL, van Gorp WG, Mitrushina M (1990) Frontal–subcortical features of normal aging: an empirical analysis. Can J Aging 9:104–119Google Scholar
  58. Izycka-Swieszewska E, Zoltowska A, Rzepko R, Gross M, Borowska-Lehman J (2000) Vasculopathy and amyloid beta reactivity in brains of patients with acquired immune deficiency (AIDS). Folia Neuropathol 38:175–182PubMedGoogle Scholar
  59. Kadiu I, Glanzer JG, Kipnis J, Gendelman HE, Thomas MP (2005) Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases. Neurotox Res 8(1–2):25–50PubMedGoogle Scholar
  60. Kemper TL (1993) The relationship of cerebral cortical changes to nuclei in the brainstem. Neurobiol Aging 14:659–660 doi:10.1016/0197-4580(93)90061-F PubMedGoogle Scholar
  61. Khanlou N, Moore DJ, Chana G, Cherner M, Lazzaretto D, Dawes S, Grant I, Masliah E, Everall IP (2008) Increased frequency of alpha-Synuclein in the substantia nigra in HIV infection. J Neurovirol (in press)Google Scholar
  62. Kitazawa M, Oddo S, Yamasaki TR, Green KN, LaFerla FM (2005) Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer’s disease. J Neurosci 25(39):8843–8853 doi:10.1523/JNEUROSCI.2868-05.2005 PubMedGoogle Scholar
  63. Kramer AF, Madden DJ (2008) Attention. In: Craik FIM, Salthouse TA (eds) The handbook of aging and cognition. Psychology, New YorkGoogle Scholar
  64. Kusdra L, Rempel H, Yaffe K, Pulliam L (2000) Elevation of CD69+ monocyte/macrophages in patients with Alzheimer’s disease. Immunobiology 202:26–33PubMedGoogle Scholar
  65. Lam F, Liu R, Shapiro AB, Renoir JM, Sharom FJ, Reiner PB (2001) B-amyloid efflux mediated by P-glycoprotein. J Neurochem 76:1121–1128 doi:10.1046/j.1471-4159.2001.00113.x PubMedGoogle Scholar
  66. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP (2008) Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 300(9):1027–1037 doi:10.1001/jama.300.9.1027 PubMedGoogle Scholar
  67. Lee G, Bendayan R (2004) Functional expression and localization of P-glycoprotein in the central nervous system: relevance to the pathogenesis and treatment of neurological disorders. Pharm Res 21(8):1313–1330 doi:10.1023/B:PHAM.0000036905.82914.8e PubMedGoogle Scholar
  68. Letendre S, McCutchan J, Childers M, Woods S, Lazzaretto D, Heaton R, Grant I, Ellis RH (2004) Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 56:416–423 doi:10.1002/ana.20198 PubMedGoogle Scholar
  69. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008) Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65–70 doi:10.1001/archneurol.2007.31 PubMedGoogle Scholar
  70. Li W, Malpica-Llanos TM, Gundry R, Cotter RJ, Sacktor N, McArthur J, Nath A (2008) Nitrosative stress with HIV dementia causes decreased L-prostaglandin D synthase activity. Neurology 70:1753–1762PubMedGoogle Scholar
  71. Lovell MA, Markesbery WR (2007) Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease. Nucleic Acids Res 35(22):7497–7504 doi:10.1093/nar/gkm821 PubMedGoogle Scholar
  72. McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P (2001) Failure of the ubiquitin–proteasome system in Parkinson’s disease. Nat Rev Neurosci 2(8):589–594 doi:10.1038/35086067 PubMedGoogle Scholar
  73. Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202:13–23 doi:10.1016/S0022-510X(02)00207-1 PubMedGoogle Scholar
  74. Mylonakis E, Koutkia P, Grinspoon S (2001) Diagnosis and treatment of androgen deficiency in human immunodeficiency virus-infected men and women. Clin Infect Dis 33(6):857–864 doi:10.1086/322695 PubMedGoogle Scholar
  75. Nagaoka U, Kim K, Jana NR, Doi H, Maruyama M, Mitsui K, Oyama F, Nukina N (2004) Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions. J Neurochem 91:57–68 doi:10.1111/j.1471-4159.2004.02692.x PubMedGoogle Scholar
  76. Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J (2008) Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 20(1):25–31 doi:10.1080/09540260701861930 PubMedGoogle Scholar
  77. Nielsen K, Peters A (2000) The effects of aging on the frequency of nerve fibers in rhesus monkey striate cortex. Neurobiol Aging 21:621–628 doi:10.1016/S0197-4580(00)00169-X PubMedGoogle Scholar
  78. Okun MS, DeLong MR, Hanfelt J, Gearing M, Levey A (2004) Plasma testosterone levels in Alzheimer and Parkinson diseases. Neurology 62(3):411–413PubMedGoogle Scholar
  79. Peavy G, Jacobs D, Salmon D, Butters N, Delis D, Taylor M, Massman P, Stout J, Heindel W, Kirson D, Atkinson J, Chandler J, Grant I (1994) Verbal memory performance of patients with human immunodeficiency virus infection: evidence of subcortical dysfunction. J Clin Exp Neuropsych 16:508–523Google Scholar
  80. Pemberton L, Brew BJ (2001) Cerebrospinal fluid S-100beta and its relationship with AIDS dementia complex. J Clin Virol 22:249–253 doi:10.1016/S1386-6532(01)00196-2 PubMedGoogle Scholar
  81. Pemberton LA, Stone E, Price P, van Bockxmeer F, Brew BJ (2008) The relationship between ApoE, TNFA, IL1a, IL1b and IL12b genes and HIV-1-associated dementia. HIV Med 9:677–680 doi:10.1111/j.1468-1293.2008.00614.x PubMedGoogle Scholar
  82. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, Waldman A, Walton I, Poulter R, Ma S, Comsa M, Burch L, Fletcher A, Bulpitt C, HYVET investigators (2007) Incident dementia and blood pressure lowering in the hypertension in the very elderly trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 7(8):683–689 doi:10.1016/S1474-4422(08)70143-1 Google Scholar
  83. 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 10:215–223PubMedGoogle Scholar
  84. Rajawat YS, Bossis I (2008) Autophagy in aging and in neurodegenerative disorders. Hormones 7(1):46–61PubMedGoogle Scholar
  85. Raz N, Rodrigue KM (2006) Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 30:730–748 doi:10.1016/j.neubiorev.2006.07.001 PubMedGoogle Scholar
  86. Reger M, Wesh R, Razani J, Martin DJ, Boone KB (2002) A meta-analysis of the neuropsychological sequelae of HIV infection. J Int Neuropsychol Soc 8:410–424 doi:10.1017/S1355617702813212 PubMedGoogle Scholar
  87. Rempel HC, Pulliam L (2005) HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS 19:127–135 doi:10.1097/00002030-200501280-00004 PubMedGoogle Scholar
  88. Richartz-Salzburger E, Batra A, Stransky E, Laske C, Köhler N, Bartels M, Buchkremer G, Schott K (2007) Altered lymphocyte distribution in Alzheimer’s disease. J Psychiatr Res 41(1–2):174–178 doi:10.1016/j.jpsychires.2006.01.010 PubMedGoogle Scholar
  89. Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915–1921 doi:10.1097/QAD.0b013e32828e4e27 PubMedGoogle Scholar
  90. Rosene DL (1993) Comparing age-related changes in the basal forebrain and hippocampus of the rhesus monkey. Neurobiol Aging 14:669–670 doi:10.1016/0197-4580(93)90065-J PubMedGoogle Scholar
  91. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69:143–179 doi:10.1016/S0301-0082(02)00126-0 PubMedGoogle Scholar
  92. Sacktor NC, Bacellar H, Hoover DR, Nance-Sproson TE, Selnes OA, Miller EN, Dal Pan GJ, Kleeberger C, Brown A, Saah A, McArthur JC (1996) Psychomotor slowing in HIV infection: a predictor of dementia, AIDS and death. J Neurovirol 2:404–410 doi:10.3109/13550289609146906 PubMedGoogle Scholar
  93. Salaria S, Badkoobehi H, Rockenstein E, Crews L, Chana G, Masliah E, Everall IP (2007) Toll-like receptor pathway gene expression is associated with human immunodeficiency virus-associated neurodegeneration. J Neurovirol 13(6):496–503 doi:10.1080/13550280701558616 PubMedGoogle Scholar
  94. Salthouse TA (1996) The processing-speed theory of adult age differences in cognition. Psychol Rev 103:403–428 doi:10.1037/0033-295X.103.3.403 PubMedGoogle Scholar
  95. Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K, Schifitto G, Selnes OA, Stern Y, McClernon DR, Palumbo D, Kieburtz K, Riggs G, Cohen B, Epstein LG, Marder K (2004) Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 63:2084–2090PubMedGoogle Scholar
  96. Sokolova A, Hill MD, Rahimi F, Warden LA, Halliday GM, Shepherd CE (2008) Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer’s disease. Brain Pathol 10:10Google Scholar
  97. Stone TW (2001) Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. Prog Neurobiol 64(2):185–218 doi:10.1016/S0301-0082(00)00032-0 PubMedGoogle Scholar
  98. Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP (2008) Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci 11(3):309–317 doi:10.1038/nn2055 PubMedGoogle Scholar
  99. Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K (2006) Role of toll-like receptor signalling in Abeta uptake and clearance. Brain 129(Pt 11):3006–3019 doi:10.1093/brain/awl249 PubMedGoogle Scholar
  100. Ting KK, Brew B, Guillemin G (2007) The involvement of astrocytes and kynurenine pathway in Alzheimer’s disease. Neurotox Res 12(4):247–262PubMedGoogle Scholar
  101. Torres-Muñoz J, Stockton P, Tacoronte N, Roberts B, Maronpot RR, Petito CK (2001) Detection of HIV-1 gene sequences in hippocampal neurons isolated from postmortem AIDS brains by laser capture microdissection. J Neuropathol Exp Neurol 60(9):885–892PubMedGoogle Scholar
  102. Town T, Laouar Y, Pittenger C, Mori T, Szekely CA, Tan J, Duman RS, Flavell RA (2008) Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 14:681–687PubMedGoogle Scholar
  103. Tucker KA, Robertson KR, Lin W, Smith JK, An H, Chen Y, Aylward SR, Hall CD (2004) Neuroimaging in human immunodeficiency virus infection. J Neuroimmunol 157:153–162 doi:10.1016/j.jneuroim.2004.08.036 PubMedGoogle Scholar
  104. Valcour V, Shikuma C, Watters M, Poff P, Selnes O, Holck P, Grove J, Sacktor N (2004) Higher frequency of dementia in older HIV-1 individuals. The Hawaii aging with HIV-1 cohort. Neurology 63:822–827PubMedGoogle Scholar
  105. Valcour V, Shiramizu B, Shikuma C (2008) Frequency of apolipoprotein E4 among older compared with younger HIV patients: support for detrimental effect of E4 on survival. Proc Natl Acad Sci U S A 8:8Google Scholar
  106. van Harten B, Oosterman J, Muslimovic D, van Loon BJ, Scheltens P, Weinstein HC (2007) Cognitive impairment and MRI correlates in the elderly patients with type 2 diabetes mellitus. Age Ageing 36(2):164–170 doi:10.1093/ageing/afl180 PubMedGoogle Scholar
  107. van Leeuwen FW, de Kleijn DP, van den Hurk HH, Neubauer A, Sonnemans MA, Sluijs JA, Koycu S, Ramdjielal RD, Salehi A, Martens GJ, Grosveld FG, Peter J, Burbach H, Hol EM (1998) Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer’s and down patients. Science 279:242–247 doi:10.1126/science.279.5348.242 PubMedGoogle Scholar
  108. van Leeuwen FW, Gerez L, Benne R, Hol EM (2002) +1 Proteins and aging. Int J Biochem Cell Biol 34:1502–1505 doi:10.1016/S1357-2725(02)00043-2 PubMedGoogle Scholar
  109. Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schuffer W, Fassbender K (2007) Role of the toll-like receptor 4 in neuroinflammation in Alzheimer’s disease. Cell Physiol Biochem 20:947–956 doi:10.1159/000110455 PubMedGoogle Scholar
  110. West RL (1996) An application of prefrontal cortex function theory to cognitive aging. Psychol Bull 120:272–292 doi:10.1037/0033-2909.120.2.272 PubMedGoogle Scholar
  111. Whitmer RA (2007) Type 2 diabetes and risk of cognitive impairment and dementia. Curr Neurol Neurosci Rep 7(5):373–380 doi:10.1007/s11910-007-0058-7 PubMedGoogle Scholar
  112. Woods SP, Iudicello JE, Moran LM, Carey CL, Dawson MS, Grant I (2008a) HIV-associated prospective memory impairment increases risk of dependence in everyday functioning. Neuropsychology 22:110–117 doi:10.1037/0894-4105.22.1.110 PubMedGoogle Scholar
  113. Woods SP, Carey CL, Ludicello JE, Letendre SL, Grant I (2008b) Neuropsychological aspects of HIV infection. In: Grant I, Adams KM (eds) Neuropsychological assessment of neuropsychiatric disorders. Oxford University Press, New York (in press)Google Scholar
  114. Wyss-Coray T (2006) Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 12(9):1005–1015PubMedGoogle Scholar
  115. Young VG, Halliday GM, Kril JJ (2008) Neuropathologic correlates of white matter hyperintensities. Neurology 71:804–811 doi:10.1212/01.wnl.0000319691.50117.54 PubMedGoogle Scholar
  116. Zatloukal K, Stumptner C, Fuchsbichler A, Heid H, Schnoelzer M, Kenner L, Kleinert R, Prinz M, Aguzzi A, Denk H (2002) p62 is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol 160:255–263PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Bruce J. Brew
    • 1
    • 2
  • S. M. Crowe
    • 3
    • 4
  • A. Landay
    • 5
  • Lucette A. Cysique
    • 1
    • 6
  • Gilles Guillemin
    • 1
    • 2
    • 7
  1. 1.Department of NeurologySt Vincent’s HospitalSydneyAustralia
  2. 2.Applied Medical Research CentreSt Vincent’s HospitalSydneyAustralia
  3. 3.Department of MedicineMonash UniversityMelbourneAustralia
  4. 4.Centre for VirologyBurnet InstituteMelbourneAustralia
  5. 5.Department of Immunology and MicrobiologyRush UniversityChicagoUSA
  6. 6.Brain Sciences InstituteUniversity of New South WalesSydneyAustralia
  7. 7.Department of PharmacologyUniversity of New South WalesSydneyAustralia

Personalised recommendations