{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:30:25Z","timestamp":1789687825792,"version":"4.0.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH099921"],"award-info":[{"award-number":["R01 MH099921"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG054328"],"award-info":[{"award-number":["R01 AG054328"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH118020"],"award-info":[{"award-number":["R01 MH118020"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. Here, we investigate the FW in HIV-infection, its temporal evolution, and its association with blood markers, and cognitive scores. Using 96 age-matched participants, we found that FW was significantly elevated in grey and white matter in cART-na\u00efve HIV+\u2009compared to HIV-uninfected (HIV\u2212) individuals at baseline. These increased FW values positively correlated with neurofilament light chain (NfL) and negatively correlated with CD4 counts. FW in grey and white matter, as well as NfL decreased in the HIV+\u2009after 12\u00a0weeks of cART treatment. No significant FW differences were noted between the HIV+\u2009and HIV\u2212 cohorts at 1 and 2-year follow-up. Results suggest that FW elevation in cART-na\u00efve HIV+\u2009participants is likely due to neuroinflammation. The correlation between FW and NfL, and the improvement in both FW and NfL after 12\u00a0weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2\u00a0years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.<\/jats:p>","DOI":"10.1038\/s41598-021-87801-y","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T10:18:05Z","timestamp":1618481885000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A longitudinal analysis of brain extracellular free water in HIV infected individuals"],"prefix":"10.1038","volume":"11","author":[{"given":"Md Nasir","family":"Uddin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar","family":"Faiyaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle D.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Descoteaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina E.","family":"Tivarus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam T.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Schifitto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"87801_CR1","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1212\/WNL.0b013e318200d727","volume":"75","author":"R Heaton","year":"2010","unstructured":"Heaton, R. et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75, 2087\u20132096 (2010).","journal-title":"Neurology"},{"key":"87801_CR2","first-page":"51","volume-title":"Advances in Immunology","author":"MM Lederman","year":"2013","unstructured":"Lederman, M. M., Funderburg, N. T., Sekaly, R. P., Klatt, N. R. & Hunt, P. W. Advances in Immunology 51\u201383 (Elsevier, Amsterdam, 2013)."},{"key":"87801_CR3","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/S0140-6736(14)60164-1","volume":"384","author":"G Maartens","year":"2014","unstructured":"Maartens, G., Celum, C. & Lewin, S. R. HIV infection: epidemiology, pathogenesis, treatment, and prevention. The Lancet 384, 258\u2013271 (2014).","journal-title":"The Lancet"},{"key":"87801_CR4","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3389\/fcimb.2019.00362","volume":"9","author":"C Wallet","year":"2019","unstructured":"Wallet, C. et al. Microglial Cells: The Main HIV-1 Reservoir in the Brain. Front. Cell. Infect. Microbiol. 9, 362. https:\/\/doi.org\/10.3389\/fcimb.2019.00362 (2019).","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"Suppl 2","key":"87801_CR5","doi-asserted-by":"publisher","first-page":"S181","DOI":"10.1097\/qad.0000000000002269","volume":"33","author":"C Abreu","year":"2019","unstructured":"Abreu, C. et al. Brain macrophages harbor latent, infectious simian immunodeficiency virus. AIDS (London, England) 33(Suppl 2), S181-s188. https:\/\/doi.org\/10.1097\/qad.0000000000002269 (2019).","journal-title":"AIDS (London, England)"},{"key":"87801_CR6","doi-asserted-by":"publisher","first-page":"e456","DOI":"10.1016\/s2352-3018(19)30143-2","volume":"6","author":"A Livelli","year":"2019","unstructured":"Livelli, A. et al. Correlates of HIV RNA concentrations in cerebrospinal fluid during antiretroviral therapy: a longitudinal cohort study. The Lancet HIV 6, e456\u2013e462. https:\/\/doi.org\/10.1016\/s2352-3018(19)30143-2 (2019).","journal-title":"The Lancet HIV"},{"key":"87801_CR7","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1097\/QAD.0b013e3283427da7","volume":"25","author":"J Harezlak","year":"2011","unstructured":"Harezlak, J. et al. Persistence of HIV\u2014associated cognitive impairment, inflammation and neuronal injury in era of highly active antiretroviral treatment. AIDS 25, 625 (2011).","journal-title":"AIDS"},{"key":"87801_CR8","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1212\/WNL.0000000000000526","volume":"82","author":"L Chang","year":"2014","unstructured":"Chang, L. et al. Effects of APOE \u03b54, age, and HIV on glial metabolites and cognitive deficits. Neurology 82, 2213\u20132222 (2014).","journal-title":"Neurology"},{"key":"87801_CR9","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1080\/13550280500187351","volume":"11","author":"DA Hammoud","year":"2005","unstructured":"Hammoud, D. A. et al. Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS. J. Neurovirol. 11, 346\u2013355 (2005).","journal-title":"J. Neurovirol."},{"key":"87801_CR10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11481-018-9823-4","volume":"14","author":"A Boerwinkle","year":"2019","unstructured":"Boerwinkle, A. & Ances, B. M. Molecular imaging of neuroinflammation in HIV. J. Neuroimmune Pharmacol. 14, 9\u201315 (2019).","journal-title":"J. Neuroimmune Pharmacol."},{"key":"87801_CR11","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1007\/s00415-017-8565-1","volume":"264","author":"AA Crawshaw","year":"2017","unstructured":"Crawshaw, A. A. & Robertson, N. P. The role of TSPO PET in assessing neuroinflammation. J. Neurol. 264, 1825\u20131827 (2017).","journal-title":"J. Neurol."},{"key":"87801_CR12","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s13139-017-0475-8","volume":"51","author":"MM Alam","year":"2017","unstructured":"Alam, M. M., Lee, J. & Lee, S.-Y. Recent progress in the development of TSPO PET ligands for neuroinflammation imaging in neurological diseases. Nucl. Med. Mol. Imaging 51, 283\u2013296 (2017).","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"87801_CR13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1097\/QAD.0000000000001314","volume":"31","author":"MJ Peluso","year":"2017","unstructured":"Peluso, M. J. et al. Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. AIDS 31, 247 (2017).","journal-title":"AIDS"},{"key":"87801_CR14","doi-asserted-by":"publisher","first-page":"e2221","DOI":"10.1212\/WNL.0000000000007449","volume":"92","author":"P Maillard","year":"2019","unstructured":"Maillard, P. et al. Cerebral white matter free water: A sensitive biomarker of cognition and function. Neurology 92, e2221\u2013e2231 (2019).","journal-title":"Neurology"},{"key":"87801_CR15","unstructured":"Guo, J. et al. Brain free water alterations in first-episode psychosis: A longitudinal analysis of diagnosis, course of illness, and medication effects. Psychol. Med. 1\u201310 (2020)."},{"key":"87801_CR16","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.jneuroim.2004.08.025","volume":"157","author":"MJ Avison","year":"2004","unstructured":"Avison, M. J. et al. Neuroimaging correlates of HIV-associated BBB compromise. J. Neuroimmunol. 157, 140\u2013146 (2004).","journal-title":"J. Neuroimmunol."},{"key":"87801_CR17","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/mrm.22055","volume":"62","author":"O Pasternak","year":"2009","unstructured":"Pasternak, O., Sochen, N., Gur, Y., Intrator, N. & Assaf, Y. Free water elimination and mapping from diffusion MRI. Magn. Reson. Med. 62, 717\u2013730 (2009).","journal-title":"Magn. Reson. Med."},{"key":"87801_CR18","doi-asserted-by":"publisher","first-page":"839","DOI":"10.3390\/cells8080839","volume":"8","author":"C Andica","year":"2019","unstructured":"Andica, C. et al. Free-water imaging in white and gray matter in Parkinson\u2019s disease. Cells 8, 839 (2019).","journal-title":"Cells"},{"key":"87801_CR19","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.schres.2014.07.031","volume":"161","author":"O Pasternak","year":"2015","unstructured":"Pasternak, O., Westin, C.-F., Dahlben, B., Bouix, S. & Kubicki, M. The extent of diffusion MRI markers of neuroinflammation and white matter deterioration in chronic schizophrenia. Schizophr. Res. 161, 113\u2013118 (2015).","journal-title":"Schizophr. Res."},{"key":"87801_CR20","doi-asserted-by":"publisher","first-page":"e0173982","DOI":"10.1371\/journal.pone.0173982","volume":"12","author":"AR Hoy","year":"2017","unstructured":"Hoy, A. R. et al. Microstructural white matter alterations in preclinical Alzheimer\u2019s disease detected using free water elimination diffusion tensor imaging. PLoS ONE 12, e0173982 (2017).","journal-title":"PLoS ONE"},{"key":"87801_CR21","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3389\/fnagi.2019.00270","volume":"11","author":"M Dumont","year":"2019","unstructured":"Dumont, M. et al. Free water in white matter differentiates MCI and AD from control subjects. Front. Aging Neurosci. 11, 270 (2019).","journal-title":"Front. Aging Neurosci."},{"key":"87801_CR22","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40035-015-0042-0","volume":"4","author":"Q Wang","year":"2015","unstructured":"Wang, Q., Liu, Y. & Zhou, J. Neuroinflammation in Parkinson\u2019s disease and its potential as therapeutic target. Transl. Neurodegener. 4, 19 (2015).","journal-title":"Transl. Neurodegener."},{"key":"87801_CR23","unstructured":"Reid B. E., et al. Examining Links Between Free Water and a TSPO-PET Marker of Neuroinflammation, Proceedings of the ISMRM 27th Annual Meeting and Exhibition 3650 (2019)."},{"key":"87801_CR24","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/0022-510X(93)90109-C","volume":"118","author":"WD Lo","year":"1993","unstructured":"Lo, W. D., Wolny, A. C., Timan, C., Shin, D. & Hinkle, G. H. Blood-brain barrier permeability and the brain extracellular space in acute cerebral inflammation. J. Neurol. Sci. 118, 188\u2013193 (1993).","journal-title":"J. Neurol. Sci."},{"key":"87801_CR25","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s00429-019-02017-1","volume":"225","author":"M Febo","year":"2020","unstructured":"Febo, M. et al. Diffusion magnetic resonance imaging-derived free water detects neurodegenerative pattern induced by interferon-\u03b3. Brain Struct. Funct. 225, 427\u2013439 (2020).","journal-title":"Brain Struct. Funct."},{"key":"87801_CR26","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.bbi.2019.09.010","volume":"83","author":"MA Di Biase","year":"2020","unstructured":"Di Biase, M. A. et al. Increased extracellular free-water in adult male rats following in utero exposure to maternal immune activation. Brain Behav. Immun. 83, 283\u2013287 (2020).","journal-title":"Brain Behav. Immun."},{"key":"87801_CR27","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1208\/s12248-014-9660-1","volume":"16","author":"J Mora","year":"2014","unstructured":"Mora, J. et al. Next generation ligand binding assays\u2014review of emerging technologies capabilities to enhance throughput and multiplexing. AAPS J. 16, 1175\u20131184 (2014).","journal-title":"AAPS J."},{"key":"87801_CR28","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1212\/01.WNL.0000287431.88658.8b","volume":"69","author":"A Antinori","year":"2007","unstructured":"Antinori, A. et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69, 1789\u20131799 (2007).","journal-title":"Neurology"},{"key":"87801_CR29","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuroimage.2011.09.015","volume":"62","author":"M Jenkinson","year":"2012","unstructured":"Jenkinson, M., Beckmann, C. F., Behrens, T. E., Woolrich, M. W. & Smith, S. M. Fsl. Neuroimage 62, 782\u2013790 (2012).","journal-title":"Neuroimage"},{"key":"87801_CR30","first-page":"1","volume":"2","author":"BB Avants","year":"2009","unstructured":"Avants, B. B., Tustison, N. & Song, G. Advanced normalization tools (ANTS). Insight J. 2, 1\u201335 (2009).","journal-title":"Insight J."},{"key":"87801_CR31","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/S1053-8119(03)00336-7","volume":"20","author":"JL Andersson","year":"2003","unstructured":"Andersson, J. L., Skare, S. & Ashburner, J. How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging. Neuroimage 20, 870\u2013888 (2003).","journal-title":"Neuroimage"},{"key":"87801_CR32","doi-asserted-by":"publisher","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","volume":"23","author":"SM Smith","year":"2004","unstructured":"Smith, S. M. et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23, S208\u2013S219 (2004).","journal-title":"Neuroimage"},{"key":"87801_CR33","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nbt.3820","volume":"35","author":"P Di Tommaso","year":"2017","unstructured":"Di Tommaso, P. et al. Nextflow enables reproducible computational workflows. Nat. Biotechnol. 35, 316 (2017).","journal-title":"Nat. Biotechnol."},{"key":"87801_CR34","doi-asserted-by":"publisher","first-page":"e0177459","DOI":"10.1371\/journal.pone.0177459","volume":"12","author":"GM Kurtzer","year":"2017","unstructured":"Kurtzer, G. M., Sochat, V. & Bauer, M. W. Singularity: Scientific containers for mobility of compute. PLoS ONE 12, e0177459 (2017).","journal-title":"PLoS ONE"},{"key":"87801_CR35","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.neuroimage.2017.08.047","volume":"161","author":"J-P Fortin","year":"2017","unstructured":"Fortin, J.-P. et al. Harmonization of multi-site diffusion tensor imaging data. Neuroimage 161, 149\u2013170 (2017).","journal-title":"Neuroimage"},{"key":"87801_CR36","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1109\/42.906424","volume":"20","author":"Y Zhang","year":"2001","unstructured":"Zhang, Y., Brady, M. & Smith, S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans. Med. Imaging 20, 45\u201357 (2001).","journal-title":"IEEE Trans. Med. Imaging"},{"key":"87801_CR37","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1080\/13803395.2014.950636","volume":"36","author":"R Kamat","year":"2014","unstructured":"Kamat, R. et al. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection. J. Clin. Exp. Neuropsychol. 36, 854\u2013866 (2014).","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"87801_CR38","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s13365-012-0135-9","volume":"19","author":"T Zhu","year":"2013","unstructured":"Zhu, T. et al. Patterns of white matter injury in HIV infection after partial immune reconstitution: A DTI tract-based spatial statistics study. J. Neurovirol. 19, 10\u201323 (2013).","journal-title":"J. Neurovirol."},{"key":"87801_CR39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. B"},{"key":"87801_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v082.i13","volume":"82","author":"A Kuznetsova","year":"2017","unstructured":"Kuznetsova, A., Brockhoff, P. B. & Christensen, R. H. B. lmerTest Package: Tests in linear mixed effects models. J. Stat. Softw. 82, 1\u201326. https:\/\/doi.org\/10.18637\/jss.v082.i13 (2017).","journal-title":"J. Stat. Softw."},{"key":"87801_CR41","doi-asserted-by":"crossref","unstructured":"Ances, B. M., Ortega, M., Vaida, F., Heaps, J. & Paul, R. Independent effects of HIV, aging, and HAART on brain volumetric measures. Journal of acquired immune deficiency syndromes (1999) 59, 469 (2012).","DOI":"10.1097\/QAI.0b013e318249db17"},{"issue":"2","key":"87801_CR42","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1097\/QAD.0000000000002404","volume":"34","author":"K Chang","year":"2020","unstructured":"Chang, K. et al. Plasma inflammatory biomarkers link to diffusion tensor imaging metrics in virally suppressed HIV-infected individuals. AIDS 34(2), 203\u2013213 (2020).","journal-title":"AIDS"},{"key":"87801_CR43","doi-asserted-by":"publisher","first-page":"17365","DOI":"10.1523\/JNEUROSCI.2904-12.2012","volume":"32","author":"O Pasternak","year":"2012","unstructured":"Pasternak, O. et al. Excessive extracellular volume reveals a neurodegenerative pattern in schizophrenia onset. J. Neurosci. 32, 17365\u201317372 (2012).","journal-title":"J. Neurosci."},{"key":"87801_CR44","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.schres.2015.05.034","volume":"173","author":"O Pasternak","year":"2016","unstructured":"Pasternak, O., Kubicki, M. & Shenton, M. E. In vivo imaging of neuroinflammation in schizophrenia. Schizophr. Res. 173, 200\u2013212 (2016).","journal-title":"Schizophr. Res."},{"key":"87801_CR45","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/s41380-019-0428-y","volume":"26","author":"TA Lesh","year":"2019","unstructured":"Lesh, T. A. et al. Extracellular free water and glutathione in first-episode psychosis\u2014a multimodal investigation of an inflammatory model for psychosis. Mol. Psychiatry 26, 761\u2013771 (2019).","journal-title":"Mol. Psychiatry"},{"key":"87801_CR46","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1177\/1352458512443092","volume":"18","author":"CE Teunissen","year":"2012","unstructured":"Teunissen, C. E. & Khalil, M. Neurofilaments as biomarkers in multiple sclerosis. Mult. Scler. J. 18, 552\u2013556 (2012).","journal-title":"Mult. Scler. J."},{"key":"87801_CR47","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ebiom.2015.11.036","volume":"3","author":"M Gissl\u00e9n","year":"2016","unstructured":"Gissl\u00e9n, M. et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: A cross-sectional study. EBioMedicine 3, 135\u2013140 (2016).","journal-title":"EBioMedicine"},{"key":"87801_CR48","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1212\/WNL.0000000000004645","volume":"89","author":"T Gattringer","year":"2017","unstructured":"Gattringer, T. et al. Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology 89, 2108\u20132114 (2017).","journal-title":"Neurology"},{"key":"87801_CR49","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neulet.2017.04.027","volume":"650","author":"W Zhou","year":"2017","unstructured":"Zhou, W. et al. Plasma neurofilament light chain levels in Alzheimer\u2019s disease. Neurosci. Lett. 650, 60\u201364 (2017).","journal-title":"Neurosci. Lett."},{"key":"87801_CR50","doi-asserted-by":"publisher","first-page":"102155","DOI":"10.1016\/j.nicl.2019.102155","volume":"25","author":"S Hassanzadeh-Behbahani","year":"2020","unstructured":"Hassanzadeh-Behbahani, S. et al. Low CD4 nadir linked to widespread cortical thinning in adults living with HIV. Neuroimage 25, 102155 (2020).","journal-title":"Neuroimage"},{"key":"87801_CR51","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1097\/QAI.0000000000001294","volume":"74","author":"R Sanford","year":"2017","unstructured":"Sanford, R. et al. Regionally specific brain volumetric and cortical thickness changes in HIV-infected patients in the HAART era. J. Acquir. Immune Defic. Syndr. 74, 563 (2017).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"87801_CR52","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1007\/s13365-019-00723-4","volume":"25","author":"TM Nir","year":"2019","unstructured":"Nir, T. M. et al. Progressive brain atrophy in chronically infected and treated HIV+ individuals. J. Neurovirol. 25, 342\u2013353 (2019).","journal-title":"J. Neurovirol."},{"key":"87801_CR53","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1093\/infdis\/jiv296","volume":"212","author":"MJ Peluso","year":"2015","unstructured":"Peluso, M. J. et al. Absence of cerebrospinal fluid signs of neuronal injury before and after immediate antiretroviral therapy in acute HIV infection. J. Infect. Dis. 212, 1759\u20131767 (2015).","journal-title":"J. Infect. Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87801-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87801-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87801-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:35:29Z","timestamp":1724844929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87801-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["87801"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-87801-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"assertion":[{"value":"22 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8273"}}