Skip to main content

Advertisement

Log in

Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid of patients infected with HIV-1 subtypes B and C

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aβ) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer’s disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and β (sAPPα, sAPPβ), Aβ oligomers 38, 40, 42, and Aβ-total; phosphorylated tau (P-tau181), and total tau (T-tau). Comparisons between HIV(+) and HIV(−) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p values were corrected for multiple testing with the Benjamini-Hochberg procedure. CSF Aβ-42 and Hulstaert (P-tau181) index were lower in HIV1-C than B (p = 0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau181 (p < 0.001), and sAPPα (p = 0.041); HIV(+) had higher CSF Aβ-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau181/Aβ-42, T-tau/Aβ-42, P-tau181/T-tau, sAPPα/β (all p ≤ 0.01) than AD. Compared to HIV(−), HIV(+) had lower CSF Aβ-42, and T-tau (all p ≤ 0.004). As conclusion, amyloid metabolism was influenced by HIV infection in a subtype-dependent manner. Aß-42 levels were lower in HIV1-C than B, suggesting that there may be greater deposition of Aß-42 in HIV1-C. These findings are supported by CSF Hulstaert (P-tau181) index. Differences between HIV and AD in the patterns of Aß and Tau biomarkers suggest that CNS HIV infection and AD may not share some of same mechanisms of neuronal injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Achim CL, Adame A, Dumaop W, Everall IP, Masliah E, Neurobehavioral Research Center (2009) Increased accumulation of intraneuronal amyloid beta in HIV-infected patients. J NeuroImmune Pharmacol 4:190–199

    Article  PubMed  PubMed Central  Google Scholar 

  • Aksenov MY, Aksenova MV, Mactutus CF, Booze RM (2010) HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures. Neurosci Lett 475:174–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almeida OP, Almeida AS (1999) Confiabilidade da versão brasileira da Escala de Depressão em Geriatria (GDS) versão reduzida. Arq Neuropsiquiatr 57:421–426

    Article  CAS  PubMed  Google Scholar 

  • de Almeida SM, Ribeiro CE, de Pereira AP, Badiee J, Cherner M, Smith D, Maich I, Raboni SM, Rotta I, Barbosa FJ, Heaton RK, Umlauf A, Ellis RJ (2013) Neurocognitive impairment in HIV-1 clade C- versus B-infected individuals in Southern Brazil. J Neuro-Oncol 19:550–556

    Google Scholar 

  • de Almeida SM, Rotta I, Jiang Y, Li X, Raboni SM, Ribeiro CE, Smith D, Potter M, Vaida F, Letendre S, Ellis RJ, HNRC Group (2016) Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B. J Neuro-Oncol 22:715–724

    Google Scholar 

  • de Almeida SM, Rotta I, Ribeiro CE, Oliveira MF, Chaillon A, de Pereira AP, Cunha AP, Zonta M, Bents JF, Raboni SM, Smith D, Letendre S, Ellis RJ (2017) Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study. J Neuro-Oncol 23:460–473

    Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association, Washington, DC

    Book  Google Scholar 

  • Ances BM, Benzinger TL, Christensen JJ, Thomas J, Venkat R, Teshome M, Aldea P, Fagan AM, Holtzman DM, Morris JC, Clifford DB (2012) 11C-PiB imaging of human immunodeficiency virus-associated neurocognitive disorder. Arch Neurol 69:72–77

    Article  PubMed  PubMed Central  Google Scholar 

  • Andersson L, Blennow K, Fuchs D, Svennerholm B, Gisslen M (1999) Increased cerebrospinal fluid protein tau concentration in neuro-AIDS. J Neurol Sci 171:92–96

    Article  CAS  PubMed  Google Scholar 

  • András IE, Toborek M (2013) Amyloid beta accumulation in HIV-1- infected brain: the role of the blood brain barrier. IUBMB Life 65:43–49

    Article  PubMed  Google Scholar 

  • András IE, Eum SY, Huang W, Zhong Y, Hennig B, Toborek M (2010) HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin. Mol Cell Neurosci 43:232–243

    Article  PubMed  Google Scholar 

  • Anoop A, Singh PK, Jacob RS, Maji SK (2010) CSF biomarkers for Alzheimer’s disease diagnosis. Int J Alzheimers Dis 2010:1–12

  • Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64:529–536

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Anthony IC, Norrby KE, Dingwall T, Dingwall T, Carnie FW, Millar T, Arango JC, Robertson R, Bell JE (2010) Predisposition to accelerated Alzheimer-related changes in the brains of human immunodeficiency virus negative opiate abusers. Brain 133:3685–3698

    Article  PubMed  Google Scholar 

  • Apcher GS, Heink S, Zantopf D, Kloetzel PM, Schmid HP, Mayer RJ, Krüger E (2003) Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal alpha and beta subunits. FEBS Lett 553:200–204

    Article  CAS  PubMed  Google Scholar 

  • Bateman RJ, Wen G, Morris JC, Holtzman DM (2007) Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker. Neurology 68:666–669

    Article  CAS  PubMed  Google Scholar 

  • Bertolucci PH, Okamoto IH, Toniolo Neto J, Ramos LR, Brucki SM (1998) Desempenho da população brasileira na bateria neuropsicológica do Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Revista de Psiquiatria Clínica 25:80–83

    Google Scholar 

  • Blennow K, Vanmechelen E (1998) Combination of the different biological markers for increasing specificity of in vivo Alzheimer’s testing. J Neural Transm Suppl 53:223–235

    Article  CAS  PubMed  Google Scholar 

  • Brasil: Ministério da Saúde (2015) Programa Nacional de DST/AIDS. http://www.aids.gov.br/assistencia/manualdst/item12.htm

  • Brew BJ, Pemberton L, Blennow K, Wallin A, Hagberg L (2005) CSF amyloid beta 42 and tau levels correlate with AIDS dementia complex. Neurology 65:1490–1492

    Article  CAS  PubMed  Google Scholar 

  • Brown LAM, Jin J, Ferrell D, Sadic E, Obregon D, Smith AJ, Tan J, Giunta B (2014) Efavirenz promotes b-secretase expression and increased Ab1-40, 42 via oxidative stress and reduced microglial phagocytosis: implications for HIV associated neurocognitive disorders (HAND). PLoS One 9(4):e95500. https://doi.org/10.1371/journal.pone.0095500

    Article  PubMed  PubMed Central  Google Scholar 

  • Brucki SM, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH (2003) Sugestões para o uso do Mini-Exame do Estado Mental no Brasil. Arq Neuropsiquiatr 61:777–781

    Article  PubMed  Google Scholar 

  • Burgoyne RW, Tan DH (2008) Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART): a balancing act. J Antimicrob Chemother 61:469–473

    Article  CAS  PubMed  Google Scholar 

  • Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR, Kauwe JS (2009) CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology 73(23):1982–1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cysique LA, Hewitt T, Croitoru-Lamoury J, Taddei K, Martins RN, Chew CSN, Davies NNWS, Price P, Brew BJ (2015) APOE ε4 moderates abnormal CSF-abeta-42 levels, while neurocognitive impairment is associated with abnormal CSF tau levels in HIV+ individuals—a cross-sectional observational study. BMC Neurol 15:51

    Article  PubMed  PubMed Central  Google Scholar 

  • Daily A, Nath A, Hersh LB (2006) Tat peptides inhibit neprilysin. J Neuro-Oncol 12:153–160

    CAS  Google Scholar 

  • Deane R, Bell RD, Sagare A, Zlokovic BV (2009) Clearance of amyloid-β peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets 8:16–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellis RJ, Seubert P, Motter R, Galasko D, Deutsch R, Heaton RK, Heyes MP, McCutchan JA, Atkinson JH, Grant I (1998) Cerebrospinal fluid tau protein is not elevated in HIV-associated neurologic disease in humans. Neurosci Lett 254(1):1–4

    Article  CAS  PubMed  Google Scholar 

  • Ensoli B, Buonaguro L, Barillari G, Fiorelli V, Gendelman R, Morgan RA, Wingfield P, Gallo RC (1993) Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol 67:277–287

    CAS  PubMed  PubMed Central  Google Scholar 

  • Esiri MM, Biddolph SC, Morris CS (1998) Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry 65:29–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 42:34–40

    Article  CAS  PubMed  Google Scholar 

  • Gisslén M, Krut J, Andreasson U, Blennow K, Cinque P, Brew BJ, Spudich S, Hagberg L, Rosengren L, Price RW, Zetterberg H (2009) Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurol 9:63

    Article  PubMed  PubMed Central  Google Scholar 

  • Giunta B, Zhou Y, Hou H, Rrapo E, Fernandez F, Tan J (2008) HIV-1 tat inhibits microglial phagocytosis of Aβ peptide. Int J Clin Exp Pathol 1:260–275

    CAS  PubMed  PubMed Central  Google Scholar 

  • Giunta B, Hou H, Zhu Y, Rrapo E, Tian J, Takashi M, Commins D, Singer E, He J, Fernandez F, Tan J (2009) HIV-1 Tat contributes to Alzheimer’s disease-like pathology in PSAPP mice. Int J Clin Exp Pathol 2:433–443

    CAS  PubMed  PubMed Central  Google Scholar 

  • Green AJ, Giovannoni G, Hall-Craggs MA, Thompson EJ, Miller RF (2000) Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological disease. Sex Transm Infect 76:443–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 19:407–411

    Article  CAS  PubMed  Google Scholar 

  • Gross AM, Jaeger PA, Kreisberg JF, Licon K, Jepsen KL, Khosroheidari M, Morsey BM, Swindells S, Shen H, Ng CT, Flagg K, Chen D, Zhang K, Fox HS, Ideker T (2016) Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Mol Cell 62:157–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamel F (2007) HIV protease inhibitors inhibit insulin-degrading enzyme (IDE) function. 67th scientific sessions. American Diabetes Association. Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β

  • Hamel FG, Fawcett J, Tsui BT, Bennett RG, Duckworth WC (2006) Effect of nelfinavir on insulin metabolism, proteasome activity and protein degradation in HepG2 cells. Diabetes Obes Metab 8:661–668

    Article  CAS  PubMed  Google Scholar 

  • Haughey NJ, Bandaru VVR, Bae M, Mattson M (2010) Roles for dysfunctional sphingolipid metabolism in Alzheimer’s disease neuropathogenesis. Biochim Biophys Acta 1801:878–886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • High KP, Brennan-Ing M, Clifford DB, Cohen MH, Currier J, Deeks SG, Deren S, Effros RB, Gebo K, Goronzy JJ, Justice AC, Landay A, Levin J, Miotti PG, Munk RJ, Nass H, Rinaldo CR Jr, Shlipak MG, Tracy R, Valcour V, Vance DE, Walston JD, Volberding P, OAR Working Group on HIV and Aging (2012) HIV and aging: state of knowledge and areas of critical need for research. A report to the NIH Office of AIDS Research by the HIV and aging working group. J Acquir Immune Defic Syndr 60(Suppl 1):S1–18

    Article  CAS  PubMed  Google Scholar 

  • Hort J, O’Brien JT, Gainotti G, Pirttila T, Popescu BO, Rektorova I, Sorbi S, Scheltens P (2010) Scientist panel on EFNS, dementia EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol 17:1236–1248

    Article  CAS  PubMed  Google Scholar 

  • Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, DeDeyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H (1999) Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology 52:1555–1562

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Yoon JH, Kim YS (2013) HIV-1 Tat interacts with and regulates the localization and processing of amyloid precursor protein. PLoS One 8(11):e77972

    Article  PubMed  PubMed Central  Google Scholar 

  • Krut JJ, Zetterberg H, Blennow K, Cinque P, Hagberg L, Price RW, Studahl M, Gisslen M (2013) Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections. J Neurol 260:620–626

    Article  CAS  PubMed  Google Scholar 

  • Krut JJ, Gisslen M, Hagberg L, Zetterberg H, Price RW, Nilsson S, Cinque P (2014) Hyperphosphorylated Tau in cerebrospinal fluid: a biomarker for neurological aging in HIV? CROI, #453

  • Lan X, Xu J, Kiyota T, Peng H, Zheng JC, Ikezu T (2011) HIV-1 reduces Abeta-degrading enzymatic activities in primary human mononuclear phagocytes. J Immunol 186:6925–6932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lan X, Kiyota T, Hanamsagar R, Huang Y, Andrews S, Peng H, Zheng JC, Swindells S, Carlson GA, Ikezu T (2012) The effect of HIV protease inhibitors on amyloid-β peptide degradation and synthesis in human cells and Alzheimer’s disease animal model. J NeuroImmune Pharmacol 7(2):412–423

    Article  PubMed  Google Scholar 

  • Letendre S, Ellis R, Deutsch R, Clifford D, Marra C, Mc Cutchan A, Morgello S, Simpson D, Heaton R, Grant I, the CHARTER Group (2010) Correlates of time-to-loss-of-viral response in CSF and plasma in the CHARTER cohort. Program and abstracts of the 17th conference on retroviruses and opportunistic infections; San Francisco, CA 16–19 February (poster) 430

  • Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, Lu B, El Mouedden M, Mercken M, Nitsch RM, Mohajeri MH (2006) Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo. J Neurosci Res 84:1871–1878

    Article  CAS  PubMed  Google Scholar 

  • Mankowski JL, Queen SE, Tarwater PM, Fox KJ, Perry VH (2002) Accumulation of beta-amyloid precursor protein in axons correlates with CNS expression of SIV gp41. J Neuropathol Exp Neurol 61:85–90

    Article  CAS  PubMed  Google Scholar 

  • Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, Bocchio-Chiavetto L, Blankenstein MA, Carrillo MC, Chalbot S, Coart E, Chiasserini D, Cutler N, Dahlfors G, Duller S, Fagan AM, Forlenza O, Frisoni GB, Galasko D, Galimberti D, Hampel H, Handberg A, Heneka MT, Herskovits AZ, Herukka SK, Holtzman DM, Humpel C, Hyman BT, Iqbal K, Jucker M, Kaeser SA, Kaiser E, Kapaki E, Kidd D, Klivenyi P, Knudsen CS, Kummer MP, Lui J, Llad’o A, Lewczuk P, Li QX, Martins R, Masters C, Mc Auliffe J, Mercken M, Moghekar A, Molinuevo JL, Montine TJ, Nowatzke W, O’Brien R, Otto M, Paraskevas GP, Parnetti L, Petersen RC, Prvulovic D, de Reus HP, Rissman RA, Scarpini E, Stefani A, Soininen H, Schr¨oder J, Shaw LM, Skinningsrud A, Skrogstad B, Spreer A, Talib L, Teunissen C, Trojanowski JQ, Tumani H, Umek RM, Van Broeck B, Vanderstichele H, Vecsei L, Verbeek MM, Windisch M, Zhang J, Zetterberg H, Blennow K (2011) The Alzheimer’s association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement 7 e6:386–395

    Article  Google Scholar 

  • McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging -Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269

    Article  PubMed  PubMed Central  Google Scholar 

  • Memória CM, Yassuda MS, Nakano EY, Forlenza OV (2013) Brief screening for mild cognitive impairment: validation of the Brazilian version of the Montreal cognitive assessment. Int J Geriatr Psychiatry 28:34–40

    Article  PubMed  Google Scholar 

  • Molinuevo JL, Gispert JD, Dubois B, Heneka MT, Lleo A, Engelborghs S, Pujol J, de Souza LC, Alcolea D, Jessen F, Sarazind M, Lamari F, Balasa M, Antonell A, Rami L (2013) The AD-CSF-index discriminates Alzheimer’s disease patients from healthy controls: a validation study. J Alzheimer’s Disease 36:67–77

    CAS  Google Scholar 

  • Mothapo K, Stelma F, Janssen M, Kessels R, Miners S, Verbeek M, Koopmans P, van der Ven A (2015) Amyloid beta-42 (Ab-42): neprilysin and cytokine levels. A pilot study in patients with HIV related cognitive impairments. J Neuroimmunol 282:73–79

    Article  CAS  PubMed  Google Scholar 

  • Nath A, Hersh LB (2005) Tat and amyloid: multiple interactions. AIDS 19:203–204

    Article  PubMed  Google Scholar 

  • Navia BA, Cho ES, Petito CK, Price RW (1986) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19(6):525–535

    Article  CAS  PubMed  Google Scholar 

  • Nebuloni M, Pellegrinelli A, Ferri A, Bonetto S, Boldorini R, Vago L, Grassi MP, Costanzi G (2001) Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients. AIDS 15(5):571–575

    Article  CAS  PubMed  Google Scholar 

  • Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, Walter R, Fuchs D, Brew BJ, Cinque P, Robertson K, Hagberg L, Zetterberg H, Gisslén M, Spudich S (2013) Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis 207(11):1703–1712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peterson J, Zetterberg H, Hagberg L, Spudich S, Gisslen M, Price R (2013) Changing CSF concentrations of neurofilament light chain, tau and amyloid proteins, characterize evolving CNS injury in HIV-1 infection. 20th Conference on Retroviruses and Opportunistic Infections, Atlanta

    Google Scholar 

  • Peterson J, Gisslen M, Zetterberg H, Fuchs D, Shacklett BL, Hagberg L, Constantin T, Yiannoutsos CT, Spudich SS, Price RW (2014) Cerebrospinal fluid (CSF) neuronal biomarkers across the Spectrum of HIV infection: hierarchy of injury and detection. PLoS One 9(12):e116081. https://doi.org/10.1371/journal.pone.0116081

    Article  PubMed  PubMed Central  Google Scholar 

  • Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S (1982) Measurement of functional activities in older adults in the community. J Gerontol 37:323–329

    Article  CAS  PubMed  Google Scholar 

  • Pulliam L (2009) HIV regulation of amyloid beta production. J NeuroImmune Pharmacol 4:213–217

    Article  PubMed  Google Scholar 

  • Raboni SM, Ribeiro CE, Almeida SM, Telles JP, Azevedo M, Schaitza GA (2017) Impact of public health strategies on reducing AIDS mortality in southern Brazil. Int J STD AIDS 28:54–62

    Article  PubMed  Google Scholar 

  • Ranga U, Shankarappa R, Siddapa NB, Ramakrishna L, Nagendran R, Mahalingam M, Mahadevan A, Jayasuryan N, Satishchandra P, Shankar SK, Prasad VR (2004) Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. J Virology 78:2586–2590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rempel HC, Pulliam L (2005) HIV-1Tat inhibits neprilysin and elevates amyloid beta. AIDS 19:127–135

    Article  CAS  PubMed  Google Scholar 

  • Satishchandra P, Nalini A, Gourie-Devi M, Khanna N, Santosh V, Rasvi V, Desai A, Chandramuki A, Jayakumar PN, Shankar SK (2000) Profile of neurologic disorders associated with HIV/AIDS from Bangalore, South India (1989-96). Indian J Med Res 111:14–23

    CAS  PubMed  Google Scholar 

  • Seeger M, Ferrell K, Frank R, Dubiel W (1997) HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation. J Biol Chem 272:8145–8148

    Article  CAS  PubMed  Google Scholar 

  • Selkoe DJ (2001) Clearing the brain’s amyloid cobwebs. Neuron 32:177–180

    Article  CAS  PubMed  Google Scholar 

  • Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, Zlokovic BV (2000) Clearance of Alzheimer’s amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 106(12):1489–1499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stanley LC, Mrak RE, Woody RC, Perrot LJ, Zhang S, Marshak DR, Nelson SJ, Griffin WS (1994) Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J Neuropathol Exp Neurol 53(3):231–238

    Article  CAS  PubMed  Google Scholar 

  • Steinbrink F, Evers S, Buerke B, Young P, Arendt G, Koutsilieri E, Reichelt D, Lohmann H, Husstedt IW (2013) Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration. Eur J Neurol 20:420–428

    Article  CAS  PubMed  Google Scholar 

  • Tran H, Robinson S, Mikhailenko I, Strickland DK (2003) Modulation of the LDL receptor and LRP levels by HIV protease inhibitors. J Lipid Res 44:1859–1869

    Article  CAS  PubMed  Google Scholar 

  • Trojanowski JQ, Schuck T, Schmidt ML, Lee VM (1989) Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem 37:209–215

    Article  CAS  PubMed  Google Scholar 

  • White JA, Manelli AM, Holmberg KH, Van Eldik LJ, Ladu MJ (2005) Differential effects of oligomeric and fibrillar amyloid-beta 1–42 on astrocyte-mediated inflammation. Neurobiol Dis 18:459–465

    Article  CAS  PubMed  Google Scholar 

  • Wood SN (2006) Generalized additive models: an introduction with R. CRC Press, LLC, Boca Raton, FL

    Google Scholar 

  • Xu J, Ikezu T (2009) The comorbidity of HIV-associated neurocognitive disorders and Alzheimer’s disease: a foreseeable medical challenge in post-HAART era. J NeuroImmune Pharmacol 4:200–212

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Liu J, Katafiasz B, Fox H, Xiong H (2011) HIV-1 gp120-induced axonal injury detected by accumulation of β-amyloid precursor protein in adult rat corpus callosum. J NeuroImmune Pharmacol 6:650–657

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the following grants: National Institute of Health, NIH R21 MH76651 (Ellis, Ronald J; Almeida, Sergio M.), S10 RR31646 (Letendre, Scott), K24 MH097673(Letendre, Scott); University of California, San Diego, Center for AIDS Research (CFAR), an NIH-funded program (P30 AI036214), which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK. The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30MH062512 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: Robert K. Heaton, Ph.D., Co-Director: Igor Grant, M.D.; Associate Directors: J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., and Scott Letendre, M.D.; Center Manager: Thomas D. Marcotte, Ph.D.; Jennifer Marquie-Beck, M.P.H.; Melanie Sherman; Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.), Scott Letendre, M.D., J. Allen McCutchan, M.D., Brookie Best, Pharm.D., Rachel Schrier, Ph.D., Debra Rosario, M.P.H.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), J. Hampton Atkinson, M.D., Steven Paul Woods, Psy.D., Thomas D. Marcotte, Ph.D., Mariana Cherner, Ph.D., David J. Moore, Ph.D., Matthew Dawson; Neuroimaging Component: Christine Fennema-Notestine, Ph.D. (P.I.), Monte S. Buchsbaum, M.D., John Hesselink, M.D., Sarah L. Archibald, M.A., Gregory Brown, Ph.D., Richard Buxton, Ph.D., Anders Dale, Ph.D., Thomas Liu, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Cristian Achim, M.D., Ph.D.; Neurovirology Component: David M. Smith, M.D. (P.I.), Douglas Richman, M.D.; International Component: J. Allen McCutchan, M.D., (P.I.), Mariana Cherner, Ph.D.; Developmental Component: Cristian Achim, M.D., Ph.D.; (P.I.), Stuart Lipton, M.D., Ph.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.), Jennifer Marquie-Beck, M.P.H.; Data Management and Information Systems Unit: Anthony C. Gamst, Ph.D. (P.I.), Clint Cushman; Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D. (Co-PI), Bin Tang, Ph.D., and Anya Umlauf, M.S.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Sérgio Monteiro de Almeida.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Almeida, S.M., Ribeiro, C.E., Rotta, I. et al. Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid of patients infected with HIV-1 subtypes B and C. J. Neurovirol. 24, 28–40 (2018). https://doi.org/10.1007/s13365-017-0591-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-017-0591-3

Keywords

Navigation