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Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders

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Abstract

HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here, we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Retrospective analysis of tissue bank specimens and pre-mortem data was carried out. Fifty-eight HIV+ adults underwent a medical and neurocognitive evaluation within 1 year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the epigenetic clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects.

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References

  • Achim CL, Adame A, Dumaop W, Everall IP, Masliah E (2009) Increased accumulation of intraneuronal amyloid beta in HIV-infected patients. J Neuroimmune Pharm 4(2):190–199

    Article  Google Scholar 

  • Alisch RS, Barwick BG, Chopra P, Myrick LK, Satten GA, Conneely KN, Warren ST (2012) Age-associated DNA methylation in pediatric populations. Genome Res 22(4):623–632. doi:10.1101/gr.125187.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M … Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69(18):1789–1799

  • Bell JT, Tsai P-C, Yang T-P, Pidsley R, Nisbet J, Glass D … The Mu TC (2012) Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet 8(4):e1002629. doi:10.1371/journal.pgen.1002629

  • Bocklandt S, Lin W, Sehl ME, Sanchez FJ, Sinsheimer JS, Horvath S, Vilain E (2011) Epigenetic predictor of age. PLoS One 6(6):e14821. doi:10.1371/journal.pone.0014821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boks MP, Derks EM, Weisenberger DJ, Strengman E, Janson E, Sommer IE … Ophoff RA (2009) The relationship of DNA methylation with age, gender and genotype in twins and healthy controls. PLoS One 4(8):e6767. doi:10.1371/journal.pone.0006767

  • Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H … Baccarelli A (2009) Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev. 130(4):234–239. doi:10.1016/j.mad.2008.12.003

  • Brew BJ, Pemberton L, Blennow K, Wallin A, Hagberg L (2005) CSF amyloid β42 and tau levels correlate with AIDS dementia complex. Neurology 65(9):1490–1492

    Article  CAS  PubMed  Google Scholar 

  • Cassol E, Misra V, Dutta A, Morgello S, Gabuzda D (2014) Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment. AIDS. doi:10.1097/QAD.0000000000000303

    PubMed  PubMed Central  Google Scholar 

  • Chang L, Holt JL, Yakupov R, Jiang CS, Ernst T (2013) Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging 34(4):1240–1253. doi:10.1016/j.neurobiolaging.2012.10.012

    Article  PubMed  Google Scholar 

  • Cherner M, Ellis RJ, Lazzaretto D, Young C, Mindt MR, Atkinson JH … Heaton RK (2004) Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS 18(Suppl 1):S27–S34

  • Christensen B, Houseman E, Marsit C, Zheng S, Wrensch M, Wiemels J … Kelsey K (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5(8):e1000602

  • Clinical confirmation of the American academy of neurology algorithm for HIV-1-associated cognitive/motor disorder. The dana consortium on therapy for hiv dementia and related cognitive disorders. (1996) Neurology 47(5):1247–1253

  • Day K, Waite L, Thalacker-Mercer A, West A, Bamman M, Brooks J … Absher D (2013) Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol 14(9):R102

  • Deeks SG (2011) HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 62(1):141–155. doi:10.1146/annurev-med-042909-093756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Desplats P, Dumaop W, Smith D, Adame A, Everall I, Letendre S … Masliah E (2013) Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology 80(15):1415–1423. doi:10.1212/WNL.0b013e31828c2e9e

  • Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, Margolick JB (2011) A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men. J Gerontol Ser A Biol Med Sci 66A(9):1030–1038. doi:10.1093/gerona/glr097

    Article  CAS  Google Scholar 

  • Dunning M, Barbosa-Morais N, Lynch A, Tavare S, Ritchie M (2008) Statistical issues in the analysis of Illumina data. BMC Bioinforma 9(1):85

    Article  Google Scholar 

  • Fausto A, Bongiovanni M, Cicconi P, Menicagli L, Ligabò EV, Melzi S … Monforte AdA (2006) Potential predictive factors of osteoporosis in HIV-positive subjects. Bone 38(6):893–897

  • Gannon P, Khan MZ, Kolson DL (2011) Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 24(3):275–283. doi:10.1097/WCO.0b013e32834695fb

    Article  PubMed  PubMed Central  Google Scholar 

  • Gelman BB, Lisinicchia JG, Chen T, Johnson KM, Jennings K, Freeman DH Jr, Soukup VM (2012) Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis. J Neuroimmune Pharm 7(3):686–700. doi:10.1007/s11481-012-9345-4

    Article  Google Scholar 

  • Gelman BB, Lisinicchia JG, Morgello S, Masliah E, Commins D, Achim CL … Soukup VM (2013) Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort. J Acquir Immune Defic Syndr 62(5):487–495. doi:10.1097/QAI.0b013e31827f1bdb

  • Giesbrecht CJ, Thornton AE, Hall-Patch C, Maan EJ, Cote HC, Money DM … Pick N (2014) Select neurocognitive impairment in HIV-infected women: associations with HIV viral load, hepatitis C virus, and depression, but not leukocyte telomere length. PLoS One 9(3):e89556. doi:10.1371/journal.pone.0089556

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Greene M, Justice AC, Lampiris HW, Valcour V (2013) Management of human immunodeficiency virus infection in advanced age. JAMA 309(13):1397–1405. doi:10.1001/jama.2013.2963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grinspoon S, Carr A (2005) Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 352(1):48–62. doi:10.1056/NEJMra041811

    Article  CAS  PubMed  Google Scholar 

  • Hannum G, Guinney J, Zhao L, Zhang L, Hughe G, Sadda S … Zhang K (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 49(2):359–367

  • Hernandez DG, Nalls MA, Gibbs JR, Arepalli S, van der Brug M, Chong S … Singleton AB (2011) Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet 20(6):1164–1172. doi:10.1093/hmg/ddq561

  • Holt JL, Kraft-Terry SD, Chang L (2012) Neuroimaging studies of the aging HIV-1-infected brain. J Neurovirol 18(4):291–302. doi:10.1007/s13365-012-0114-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horvath S (2013a) DNA methylation age of human tissues and cell types. Genome Biol 14(10):R115. doi:10.1186/gb-2013-14-10-r115

    Article  PubMed  PubMed Central  Google Scholar 

  • Horvath S (2013b) Webpage: http://labs.genetics.ucla.edu/horvath/dnamage

  • Horvath S, Levine AJ (2015) HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis. doi:10.1093/infdis/jiv277

    PubMed  PubMed Central  Google Scholar 

  • Horvath S, Zhang Y, Langfelder P, Kahn R, Boks M, van Eijk K … Ophoff RA (2012) Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol 13:R97

  • Horvath S, Erhart W, Brosch M, Ammerpohl O, von Schonfels W, Ahrens M … Hampe J (2014) Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci USA 111(43):15538–15543. doi:10.1073/pnas.1412759111

  • Horvath S, Garagnani P, Bacalini MG, Pirazzini C, Salvioli S, Gentilini D … Franceschi C (2015a) Accelerated epigenetic aging in Down syndrome. Aging Cell 14(3):491–495. doi:10.1111/acel.12325

  • Horvath S, Mah V, Lu AT, Woo JS, Choi OW, Jasinska AJ … Coles LS (2015b) The cerebellum ages slowly according to the epigenetic clock. Aging (Albany NY) 7(5):294–306

  • Jaffe A, Irizarry R (2014) Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol 15(2):R31

    Article  PubMed  PubMed Central  Google Scholar 

  • Johansson A, Enroth S, Gyllensten U (2013) Continuous aging of the human DNA methylome throughout the human lifespan. PLoS One 8(6):e67378. doi:10.1371/journal.pone.0067378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung M, Pfeifer GP (2015) Aging and DNA methylation. BMC Biol 13:7. doi:10.1186/s12915-015-0118-4

    Article  PubMed  PubMed Central  Google Scholar 

  • Kallianpur AR, Levine AJ (2014) Host genetic factors predisposing to HIV-associated neurocognitive disorder. Curr HIV/AIDS Rep. doi:10.1007/s11904-014-0222-z

    PubMed  PubMed Central  Google Scholar 

  • Kazantsev AG, Thompson LM (2008) Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 7(10):854–868. doi:10.1038/nrd2681

    Article  CAS  PubMed  Google Scholar 

  • Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y … Thomas DL (2013) HIV, age, and the severity of hepatitis C virus–related liver disease A cohort study. Ann Intern Med. doi:10.7326/0003-4819-158-9-201305070-00604

  • Kraft-Terry SD, Buch SJ, Fox HS, Gendelman HE (2009) A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection. Neuron 64(1):133–145. doi:10.1016/j.neuron.2009.09.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Letendre S (2011) Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med 19(4):137–142

    PubMed  PubMed Central  Google Scholar 

  • Levine AJ, Horvath S, Miller EN, Singer EJ, Shapshak P, Baldwin GC, Martínez-Maza O, Witt MD, Langfelder P (2013a) Transcriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning. J Neuroimmunol 265(1–2):96–105. doi:10.1016/j.jneuroim.2013.09.016

    Article  CAS  PubMed  Google Scholar 

  • Levine AJ, Miller JA, Shapshak P, Gelman B, Singer EJ, Hinkin CH, Commins D, Morgello S, Grant I, Horvath S (2013b) Systems analysis of human brain gene expression: mechanisms for HIV-associated neurocognitive impairment and common pathways with Alzheimer’s disease. BMC Med Genomics 6(1):4. doi:10.1186/1755-8794-6-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine AJ, Panos SE, Horvath S (2014) Genetic, transcriptomic, and epigenetic studies of HIV-associated neurocognitive disorder. J Acquir Immune Defic Syndr 65(4):481–503. doi:10.1097/QAI.0000000000000069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lucas GM, Mehta SH, Atta MG, Kirk GD, Galai N, Vlahov D, Moore RD (2007) End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004. AIDS 21(18):2435–2443

    Article  PubMed  Google Scholar 

  • Malan-Muller S, Hemmings SM, Spies G, Kidd M, Fennema-Notestine C, Seedat S (2013) Shorter telomere length–a potential susceptibility factor for HIV-associated neurocognitive impairments in South African women [corrected]. PLoS One 8(3):e58351. doi:10.1371/journal.pone.0058351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE … Deary IJ (2015a) DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol 16:25. doi:10.1186/s13059-015-0584-6

  • Marioni RE, Shah S, McRae AF, Ritchie SJ, Muniz-Terrera G, Harris SE … Deary IJ (2015b) The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol. doi:10.1093/ije/dyu277

  • Martin J, Volberding P (2010) HIV and premature aging: a field still in its infancy. Ann Intern Med 153(7):477–479. doi:10.7326/0003-4819-153-7-201010050-00013

    Article  PubMed  Google Scholar 

  • Migliore L, Coppede F (2009) Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases. Mutat Res 667(1–2):82–97. doi:10.1016/j.mrfmmm.2008.10.011

    Article  CAS  PubMed  Google Scholar 

  • Morgello S, Gelman B, Kozlowski P, Vinters H, Masliah E, Cornford M … Singer E (2001) The national neuroAIDS tissue consortium: a new paradigm in brain banking with an emphasis on infectious disease. Neuropathol Appl Neurobiol 27(4):326–335

  • Mukerjee R, Chang JR, Del Valle L, Bagashev A, Gayed MM, Lyde RB … Sawaya BE (2011) Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders. J Biol Chem 286(40):34976–34985. doi:10.1074/jbc.M111.241547

  • Narasipura SD, Kim S, Al-Harthi L (2014) Epigenetic regulation of HIV-1 latency in astrocytes. J Virol 88(5):3031–3038. doi:10.1128/JVI.03333-13

    Article  PubMed  PubMed Central  Google Scholar 

  • Numata S, Ye T, Hyde, Thomas M, Guitart-Navarro X, Tao R, Wininger M … Lipska, Barbara K (2012) DNA methylation signatures in development and aging of the human prefrontal cortex. Am J Hum Genet 90(2):260–272. doi:10.1016/j.ajhg.2011.12.020

  • Ojeda D, Lopez-Costa JJ, Sede M, Lopez EM, Berria MI, Quarleri J (2014) Increased in vitro glial fibrillary acidic protein expression, telomerase activity, and telomere length after productive human immunodeficiency virus-1 infection in murine astrocytes. J Neurosci Res 92(2):267–274. doi:10.1002/jnr.23294

    Article  CAS  PubMed  Google Scholar 

  • Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Coffin JM (2003) New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 41(10):4531–4536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pendyala G, Fox HS (2010) Proteomic and metabolomic strategies to investigate HIV-associated neurocognitive disorders. Genome Med 2(3):22. doi:10.1186/gm143

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez-Santiago J, Plongthongkum N, Letendre S, Ellis R, Gouaux B, Moore D, LeBlanc S, Rajagopal N, Zhang K, Woelk C (2012) DNA methylation correlates with neurological decline in HIV-infected individuals. Paper presented at the 19th conference on retroviruses and opportunistic infections. Seattle, Washington

    Google Scholar 

  • Pulliam L, Rempel H, Sun B, Abadjian L, Calosing C, Meyerhoff DJ (2011) A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations. AIDS 25(14):1721–1726. doi:10.1097/QAD.0b013e328349f022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, Beyan H … Spector TD (2010) Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20(4):434–439. doi:10.1101/gr.103101.109

  • Saiyed ZM, Gandhi N, Agudelo M, Napuri J, Samikkannu T, Reddy PV … Nair MP (2011) HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: implication for HIV-associated neurocognitive disorder (HAND). Neurochem Int 58(6):656–664. doi:10.1016/j.neuint.2011.02.004

  • Silverberg M, Chao C, Leyden W, Xu L, Tang B, Horberg M … Abrams D (2009) HIV infection and the risk of cancers with and without a known infectious cause. AIDS 23(17):2337–2345. doi:10.1097/QAD.0b013e3283319184

  • Silverberg MJ, Chao C, Leyden WA, Xu L, Horberg MA, Klein D … Abrams DI (2011) HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomarkers Prev 20(12):2551–2559. doi:10.1158/1055-9965.epi-11-0777

  • Soontornniyomkij V, Risbrough VB, Young JW, Wallace CK, Soontornniyomkij B, Jeste DV, Achim CL (2010) Short-term recognition memory impairment is associated with decreased expression of FK506 binding protein 51 in the aged mouse brain. Age (Dordr) 32(3):309–322. doi:10.1007/s11357-010-9145-9

    Article  CAS  Google Scholar 

  • Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A, Masliah E, Levine AJ, Singer EJ, Vinters HV, Gelman BB, Morgello S, Cherner M, Grant I, Achim CL (2012a) Cerebral beta-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE epsilon4 carriers. AIDS 26(18):2327–2335. doi:10.1097/QAD.0b013e32835a117c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soontornniyomkij V, Soontornniyomkij B, Moore DJ, Gouaux B, Masliah E, Tung S, Vinters HV, Grant I, Achim CL (2012b) Antioxidant sestrin-2 redistribution to neuronal soma in human immunodeficiency virus-associated neurocognitive disorders. J Neuroimmune Pharmacol 7(3):579–590. doi:10.1007/s11481-012-9357-0

  • Sun JM, Spencer VA, Chen HY, Li L, Davie JR (2003) Measurement of histone acetyltransferase and histone deacetylase activities and kinetics of histone acetylation. Methods 31(1):12–23

    Article  CAS  PubMed  Google Scholar 

  • Tatro ET, Scott ER, Nguyen TB, Salaria S, Banerjee S, Moore DJ … Everall IP (2010) Evidence for alteration of gene regulatory networks through microRNAs of the HIV-infected brain: novel analysis of retrospective cases. PLoS One 5(4):e10337. doi:10.1371/journal.pone.0010337

  • Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, Shen H … Widschwendter M (2010) Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res 20(4):440–446. doi:10.1101/gr.103606.109

  • Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, Beck S (2013) A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics 29(2):189–196. doi:10.1093/bioinformatics/bts680

    Article  CAS  PubMed  Google Scholar 

  • Thomas J (1999) Doherty SM (2003) HIV infection–a risk factor for osteoporosis. J Acquir Immune Defic Syndr 33(3):281–291

    Article  Google Scholar 

  • Toggas SM, Mucke L (1996) Transgenic models in the study of AIDS dementia complex. Curr Top Microbiol Immunol 206:223–241

    CAS  PubMed  Google Scholar 

  • Triant VA, Lee H, Hadigan C, Grinspoon SK (2007) Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 92(7):2506–2512. doi:10.1210/jc.2006-2190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wendelken L, Valcour V (2012) Impact of HIV and aging on neuropsychological function. J Neurovirol 18(4):256–263. doi:10.1007/s13365-012-0094-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Winkler JM, Chaudhuri AD, Fox HS (2012) Translating the brain transcriptome in neuroAIDS: from non-human primates to humans. J Neuroimmune Pharm 7(2):372–379. doi:10.1007/s11481-012-9344-5

    Article  Google Scholar 

  • Womack JA, Goulet JL, Gibert C, Brandt C, Chang CC, Gulanski B … for the Veterans Aging Cohort Study Project T (2011) Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS One 6(2):e17217. doi:10.1371/journal.pone.0017217

  • Yuan T, Jiao Y, de Jong S, Ophoff RA, Beck S, Teschendorff AE (2015) An integrative multi-scale analysis of the dynamic DNA methylation landscape in aging. PLoS Genet 11(2):e1004996. doi:10.1371/journal.pgen.1004996

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Research results presented in this review were made possible by the following NIH grants: R01MH096648; National Neurological AIDS Bank (U24MH100929, 1U01MH083500, and R24-NS38841); California NeuroAIDS Tissue Network (U24-MH100928 and R24-MH59745); and the University of California–Los Angeles Center for AIDS Research/Clinical and Translational Science Institute grant (UL1TR000124). Our deepest gratitude to the volunteers enrolled in the National Neurological AIDS Bank and California NeuroAIDS Tissue Network. Our thanks to Ben Gouaux, Seth Sherman, and Lucas Barwick for their assistance in compiling the data.

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Authors and Affiliations

  1. Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Andrew J. Levine, Elyse J. Singer & Natasha Nemanim

  2. Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Austin Quach

  3. Department of Psychiatry, San Diego School of Medicine, University of California, La Jolla, CA, USA

    David J. Moore, Cristian L. Achim & Virawudh Soontornniyomkij

  4. Departments of Neuroscience and Pathology, San Diego School of Medicine, University of California, La Jolla, CA, USA

    Eliezer Masliah

  5. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

    Benjamin Gelman

  6. Departments of Human Genetics and Biostatistics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Steve Horvath

  7. UCLA–Reed Neurological Research Center, 710 Westwood Plaza, Room 2-250, Los Angeles, CA, 90095, USA

    Andrew J. Levine

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Levine, A.J., Quach, A., Moore, D.J. et al. Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders. J. Neurovirol. 22, 366–375 (2016). https://doi.org/10.1007/s13365-015-0406-3

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