Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: Hierarchy of injury and detection

PLoS ONE

Volumn 9, Issue 12, 2014, Pages

  Peterson, Julia ^a   Gisslen, Magnus ^b   Zetterberg, Henrik ^c,d   Fuchs, Dietmar ^e   Shacklett, Barbara L ^f   Hagberg, Lars ^b   Yiannoutsos, Constantin T ^g   Spudich, Serena S ^h   Price, Richard W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c UNIVERSITY OF GOTHENBURG   (Sweden)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

^e INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g INDIANA UNIVERSITY   (United States)

^h YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-38]; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; AMYLOID PRECURSOR PROTEIN ALPHA; AMYLOID PRECURSOR PROTEIN BETA; BIOLOGICAL MARKER; NEUROFILAMENT LIGHT CHAIN PROTEIN; NEUROFILAMENT PROTEIN; TAU PROTEIN; UNCLASSIFIED DRUG; VIRUS RNA; NEUROFILAMENT PROTEIN L; PEPTIDE FRAGMENT;

ADULT; ALZHEIMER DISEASE; ARTICLE; CD4+ T LYMPHOCYTE; CENTRAL NERVOUS SYSTEM INFECTION; CEREBROSPINAL FLUID ANALYSIS; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DEGENERATIVE DISEASE; DISEASE COURSE; EXPLORATORY RESEARCH; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MALE; NERVE INJURY; PATHOPHYSIOLOGY; PATIENT CARE; PATIENT CODING; PROTEIN CEREBROSPINAL FLUID LEVEL; PROTEIN PHOSPHORYLATION; SENSITIVITY ANALYSIS; VIRUS INHIBITION; VIRUS LOAD; CEREBROSPINAL FLUID; COMPLICATION; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS; ISOLATION AND PURIFICATION; MIDDLE AGED; NEUROLOGIC DISEASE; PHOSPHORYLATION;

ADULT; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; BIOMARKERS; CROSS-SECTIONAL STUDIES; FEMALE; HIV; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; NERVOUS SYSTEM DISEASES; NEUROFILAMENT PROTEINS; PEPTIDE FRAGMENTS; PHOSPHORYLATION; TAU PROTEINS;

EID: 84919884406     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0116081     Document Type: Article

References (94)

1. Davis LE, Hjelle BL, Miller VE, Palmer DL, Llewellyn AL, et al. (1992) Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 42: 1736-1739.
2. Spudich S, Gisslen M, Hagberg L, Lee E, Liegler T, et al. (2011) Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden. The Journal of infectious diseases 204: 753-760.
3. Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, et al. (2012) Central nervous system viral invasion and inflammation during acute HIV infection. The Journal of infectious diseases 206: 275-282.
4. Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, et al. (2013) Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection. The Journal of infectious diseases 207: 1703-1712.
5. Ellis RJ, Hsia K, Spector SA, Nelson JA, Heaton RK, et al. (1997) Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group. Annals of neurology 42: 679-688.
6. McArthur JC, McClernon DR, Cronin MF, Nance-Sproson TE, Saah AJ, et al. (1997) Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Annals of neurology 42: 689-698.
7. Gisslen M, Fuchs D, Svennerholm B, Hagberg L (1999) Cerebrospinal fluid viral load, intrathecal immunoactivation, and cerebrospinal fluid monocytic cell count in HIV-1 infection. Journal of acquired immune deficiency syndromes 21: 271-276.
8. Spudich SS, Nilsson AC, Lollo ND, Liegler TJ, Petropoulos CJ, et al. (2005) Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC infectious diseases 5: 98.
9. Schnell G, Joseph S, Spudich S, Price RW, Swanstrom R (2011) HIV-1 replication in the central nervous system occurs in two distinct cell types. PLoS pathogens 7: e1002286.
10. Price RW, Spudich SS, Peterson J, Joseph S, Fuchs D, et al. (2014) Evolving character of chronic central nervous system HIV infection. Semin Neurol 34: 7-13.
11. Navia BA, Jordan BD, Price RW (1986) The AIDS dementia complex: I. Clinical features. Annals of neurology 19: 517-524.
12. Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, et al. (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239: 586-592.
13. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, et al. (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69: 1789-1799.
14. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, et al. (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. Journal of neurovirology 17: 3-16.
15. Arrildt KT, Joseph SB, Swanstrom R (2012) The HIV-1 env protein: a coat of many colors. Current HIV/AIDS reports 9: 52-63.
16. d'Arminio Monforte A, Cinque P, Mocroft A, Goebel FD, Antunes F, et al. (2004) Changing incidence of central nervous system diseases in the EuroSIDA cohort. Ann Neurol 55: 320-328.
17. Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, et al. (2008) Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Annals of neurology 63: 213-221.
18. Lescure FX, Omland LH, Engsig FN, Roed C, Gerstoft J, et al. (2011) Incidence and impact on mortality of severe neurocognitive disorders in persons with and without HIV infection: a Danish nationwide cohort study. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 52: 235-243.
19. Yarchoan R, Berg G, Brouwers P, Fischl MA, Spitzer AR, et al. (1987) Response of human-immunodeficiency- virus-associated neurological disease to 3′-azido-3′-deoxythymidine. Lancet 1: 132-135.
20. Sidtis JJ, Gatsonis C, Price RW, Singer EJ, Collier AC, et al. (1993) Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group. Annals of neurology 33: 343-349.
21. Tozzi V, Balestra P, Galgani S, Narciso P, Ferri F, et al. (1999) Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment. AIDS 13: 1889-1897.
22. Price RW, Spudich S (2008) Antiretroviral therapy and central nervous system HIV type 1 infection. The Journal of infectious diseases 197 Suppl 3: S294-306.
23. Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, et al. (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24: 1243-1250.
24. Ellis RJ, Badiee J, Vaida F, Letendre S, Heaton RK, et al. (2011) CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 25: 1747-1751.
25. Eden A, Price RW, Spudich S, Fuchs D, Hagberg L, et al. (2007) Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy. The Journal of infectious diseases 196: 1779-1783.
26. Dahl V, Peterson J, Fuchs D, Gisslen M, Palmer S, et al. (2014) Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS.
27. Price RW, Brew BJ (1988) The AIDS dementia complex. J Infect Dis 158: 1079-1083.
28. (1991) Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Report of a Working Group of the American Academy of Neurology AIDS Task Force. Neurology 41: 778-785.
29. Sidtis JJ (1994) Evaluation of the AIDS dementia complex in adults. Research publications - Association for Research in Nervous and Mental Disease 72: 273-287.
30. Post MJ, Berger JR, Quencer RM (1991) Asymptomatic and neurologically symptomatic HIV-seropositive individuals: prospective evaluation with cranial MR imaging. Radiology 178: 131-139.
31. Ernst T, Yakupov R, Nakama H, Crocket G, Cole M, et al. (2009) Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 65: 316-325.
32. Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, et al. (2011) Clinical factors related to brain structure in HIV: the CHARTER study. Journal of neurovirology 17: 248-257.
33. Ances BM, Ortega M, Vaida F, Heaps J, Paul R (2012) Independent effects of HIV, aging, and HAART on brain volumetric measures. Journal of acquired immune deficiency syndromes 59: 469-477.
34. Risacher SL, Saykin AJ (2013) Neuroimaging biomarkers of neurodegenerative diseases and dementia. Semin Neurol 33: 386-416.
35. Hua X, Boyle CP, Harezlak J, Tate DF, Yiannoutsos CT, et al. (2013) Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment. Neuroimage Clin 3: 132-142.
36. Zhu T, Zhong J, Hu R, Tivarus M, Ekholm S, et al. (2013) Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study. J Neurovirol 19: 10-23.
37. Vazeux R, Brousse N, Jarry A, Henin D, Marche C, et al. (1987) AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol 126: 403-410.
38. Rosenblum MK (1990) Infection of the central nervous system by the human immunodeficiency virus type 1. Morphology and relation to syndromes of progressive encephalopathy and myelopathy in patients with AIDS. Pathol Annu 25 Pt 1: 117-169.
39. Budka H (1991) Neuropathology of human immunodeficiency virus infection. Brain Pathol 1: 163-175.
40. Masliah E, Ge N, Achim CL, DeTeresa R, Wiley CA (1996) Patterns of neurodegeneration in HIV encephalitis. Journal of neuro-AIDS 1: 161-173.
41. Gelman BB, Lisinicchia JG, Morgello S, Masliah E, Commins D, et al. (2013) Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort. Journal of acquired immune deficiency syndromes 62: 487-495.
42. Bonnet F, Amieva H, Marquant F, Bernard C, Bruyand M, et al. (2013) Cognitive disorders in HIV-infected patients: are they HIV-related? AIDS 27: 391-400.
43. Gisslen M, Price RW, Nilsson S (2011) The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence? BMC infectious diseases 11: 356.
44. Meyer AC, Boscardin WJ, Kwasa JK, Price RW (2013) Is it time to rethink how neuropsychological tests are used to diagnose mild forms of HIV-associated neurocognitive disorders? Impact of false-positive rates on prevalence and power. Neuroepidemiology 41: 208-216.
45. Gisslen M, Hagberg L, Rosengren L, Brew BJ, Cinque P, et al. (2007) Defining and evaluating HIV-related neurodegenerative disease and its treatment targets: a combinatorial approach to use of cerebrospinal fluid molecular biomarkers. Journal of neuroimmune pharmacology: the official journal of the Society on NeuroImmune Pharmacology 2: 112-119.
46. Gisslen M, Krut J, Andreasson U, Blennow K, Cinque P, et al. (2009) Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC neurology 9: 63.
47. Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, et al. (2009) CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology 73: 1982-1987.
48. Krut JJ, Zetterberg H, Blennow K, Cinque P, Hagberg L, et al. (2013) Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections. Journal of neurology 260: 620-626.
49. Price RW, Peterson J, Fuchs D, Angel TE, Zetterberg H, et al. (2013) Approach to cerebrospinal fluid (CSF) biomarker discovery and evaluation in HIV infection. J Neuroimmune Pharmacol 8: 1147-1158.
50. Mellgren A, Price RW, Hagberg L, Rosengren L, Brew BJ, et al. (2007) Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection. Neurology 69: 1536-1541.
51. Gisslen M, Hagberg L, Brew BJ, Cinque P, Price RW, et al. (2007) Elevated cerebrospinal fluid neurofilament light protein concentrations predict the development of AIDS dementia complex. The Journal of infectious diseases 195: 1774-1778.
52. Jessen Krut J, Mellberg T, Price RW, Hagberg L, Fuchs D, et al. (2014) Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients. PLoS One 9: e88591.
53. Saag M, Deeks SG (2010) How do HIV elite controllers do what they do? Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 51: 239-241.
54. Probasco JC, Deeks SG, Lee E, Hoh R, Hunt PW, et al. (2010) Cerebrospinal fluid in HIV-1 systemic viral controllers: absence of HIV-1 RNA and intrathecal inflammation. AIDS 24: 1001-1005.
55. Dahl V, Peterson J, Spudich S, Lee E, Shacklett BL, et al. (2013) Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers. AIDS 27: 1145-1149.
56. Landqvist Waldo M, Frizell Santillo A, Passant U, Zetterberg H, Rosengren L, et al. (2013) Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia. BMC Neurol 13: 54.
57. Gunnarsson M, Malmestrom C, Axelsson M, Sundstrom P, Dahle C, et al. (2011) Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Annals of neurology 69: 83-89.
58. Constantinescu R, Rosengren L, Johnels B, Zetterberg H, Holmberg B (2010) Consecutive analyses of cerebrospinal fluid axonal and glial markers in Parkinson's disease and atypical Parkinsonian disorders. Parkinsonism Relat Disord 16: 142-145.
59. Constantinescu R, Holmberg B, Rosengren L, Corneliusson O, Johnels B, et al. (2011) Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease. Acta Neurol Scand 124: 206-210.
60. Abdulle S, Mellgren A, Brew BJ, Cinque P, Hagberg L, et al. (2007) CSF neurofilament protein (NFL) - a marker of active HIV-related neurodegeneration. Journal of neurology 254: 1026-1032.
61. Sjogren M, Davidsson P, Tullberg M, Minthon L, Wallin A, et al. (2001) Both total and phosphorylated tau are increased in Alzheimer's disease. J Neurol Neurosurg Psychiatry 70: 624-630.
62. Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6: 131-144.
63. Hampel H, Blennow K, Shaw LM, Hoessler YC, Zetterberg H, et al. (2010) Total and phosphorylated tau protein as biological markers of Alzheimer's disease. Exp Gerontol 45: 30-40.
64. 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.
65. Andreasson U, Portelius E, Andersson ME, Blennow K, Zetterberg H (2007) Aspects of beta-amyloid as a biomarker for Alzheimer's disease. Biomark Med 1: 59-78.
66. Zetterberg H, Mattsson N (2014) Understanding the cause of sporadic Alzheimer's disease. Expert Rev Neurother 14: 621-630.
67. 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.
68. 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.
69. Ortega M, Ances BM (2014) Role of HIV in Amyloid Metabolism. J Neuroimmune Pharmacol.
70. Zetterberg H, Andreasson U, Hansson O, Wu G, Sankaranarayanan S, et al. (2008) Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Archives of neurology 65: 1102-1107.
71. Lewczuk P, Kamrowski-Kruck H, Peters O, Heuser I, Jessen F, et al. (2010) Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study. Mol Psychiatry 15: 138-145.
72. Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, et al. (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58: 1-207; quiz CE201-204.
73. Ho EL, Ronquillo R, Altmeppen H, Spudich SS, Price RW, et al. (2013) Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects. PloS one 8: e66188.
74. Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelso C (1996) Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem 67: 2013-2018.
75. Rosengren LE, Karlsson JE, Sjogren M, Blennow K, Wallin A (1999) Neurofilament protein levels in CSF are increased in dementia. Neurology 52: 1090-1093.
76. Norgren N, Rosengren L, Stigbrand T (2003) Elevated neurofilament levels in neurological diseases. Brain research 987: 25-31.
77. Gunnarsson M, Malmestrom C, Axelsson M, Sundstrom P, Dahle C, et al. (2011) Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 69: 83-89.
78. Dotevall L, Hagberg L, Karlsson JE, Rosengren LE (1999) Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis. Eur J Neurol 6: 169-178.
79. Studahl M, Rosengren L, Gunther G, Hagberg L (2000) Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. Journal of neurology 247: 636-642.
80. Quintanar JL, Franco LM, Salinas E (2003) Detection of glial fibrillary acidic protein and neurofilaments in the cerebrospinal fluid of patients with neurocysticercosis. Parasitol Res 90: 261-263.
81. Mattsson N, Bremell D, Anckarsater R, Blennow K, Anckarsater H, et al. (2010) Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism. BMC Neurol 10: 51.
82. Grahn A, Hagberg L, Nilsson S, Blennow K, Zetterberg H, et al. (2013) Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections. Journal of neurology 260: 1813-1821.
83. Hoffman PN, Cleveland DW, Griffin JW, Landes PW, Cowan NJ, et al. (1987) Neurofilament gene expression: a major determinant of axonal caliber. Proc Natl Acad Sci U S A 84: 3472-3476.
84. Gray F, Adle-Biassette H, Chretien F, Lorin de la Grandmaison G, Force G, et al. (2001) Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments. Clin Neuropathol 20: 146-155.
85. Murray ME, Kouri N, Lin WL, Jack CR Jr, Dickson DW, et al. (2014) Clinicopathologic assessment and imaging of tauopathies in neurodegenerative dementias. Alzheimers Res Ther 6: 1.
86. Ortega M, Ances BM (2014) Role of HIV in Amyloid Metabolism. Journal of neuroimmune pharmacology: the official journal of the Society on NeuroImmune Pharmacology.
87. Nebuloni M, Pellegrinelli A, Ferri A, Bonetto S, Boldorini R, et al. (2001) Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients. AIDS 15: 571-575.
88. 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. Journal of neuropathology and experimental neurology 61: 85-90.
89. Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, et al. (2010) Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 50: 773-778.
90. Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, et al. (2012) Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS 26: 1765-1774.
91. Price RW, Paxinos EE, Grant RM, Drews B, Nilsson A, et al. (2001) Cerebrospinal fluid response to structured treatment interruption after virological failure. AIDS 15: 1251-1259.
92. Price RW, Sidtis JJ (1990) Evaluation of the AIDS dementia complex in clinical trials. Journal of acquired immune deficiency syndromes 3 Suppl 2: S51-60.
93. Price RW, Yiannoutsos CT, Clifford DB, Zaborski L, Tselis A, et al. (1999) Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium study team. AIDS 13: 1677-1685.
94. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, et al. (2006) Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5: 228-234.