{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T22:53:40Z","timestamp":1774047220466,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Recent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer\u2019s Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.<\/jats:p>","DOI":"10.3390\/cells9122556","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:55:31Z","timestamp":1606686931000},"page":"2556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hearing Loss in Alzheimer\u2019s Disease Is Associated with Altered Serum Lipidomic Biomarker Profiles"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-1837","authenticated-orcid":false,"given":"Daniel","family":"Llano","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Carle Neuroscience Institute, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-8668","authenticated-orcid":false,"given":"Lina","family":"Issa","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya","family":"Devanarayan","sequence":"additional","affiliation":[{"name":"Department of Biology and Schreyer Honors College, Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viswanath","family":"Devanarayan","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, PA 19426 USA"},{"name":"Department of Mathematics, Statistics and Computer Science, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1001\/archoto.2011.15","article-title":"The prevalence of hearing impairment and associated risk factors: The Beaver Dam Offspring Study","volume":"137","author":"Nash","year":"2011","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"ref_3","unstructured":"Ortman, J.M., Velkoff, V.A., and Hogan, H. (2014). An Aging Nation: The Older Population in the United States, United States Census Bureau, Economics and Statistics Administration."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1037\/a0024238","article-title":"Hearing loss and cognition in the Baltimore Longitudinal Study of Aging","volume":"25","author":"Lin","year":"2011","journal-title":"Neuropsychology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/archneurol.2010.362","article-title":"Hearing loss and incident dementia","volume":"68","author":"Lin","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1093\/gerona\/glr002","article-title":"Hearing loss prevalence and risk factors among older adults in the United States","volume":"66","author":"Lin","year":"2011","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1001\/jamainternmed.2013.1868","article-title":"Hearing loss and cognitive decline in older adults","volume":"173","author":"Lin","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/lio2.65","article-title":"Hearing loss as a risk factor for dementia: A systematic review","volume":"2","author":"Thomson","year":"2017","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1111\/jgs.14848","article-title":"Observed hearing loss and incident dementia in a multiethnic cohort","volume":"65","author":"Golub","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/nrneurol.2015.12","article-title":"Age-related hearing impairment\u2014A risk factor and frailty marker for dementia and AD","volume":"11","author":"Panza","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.maturitas.2018.03.004","article-title":"Hearing loss and the risk of dementia in later life","volume":"112","author":"Ford","year":"2018","journal-title":"Maturitas"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nadhimi, Y., and Llano, D.A. (2020). Does hearing loss lead to dementia? A review of the literature. Hear. Res., 108038.","DOI":"10.31234\/osf.io\/zgkvr"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"582849","DOI":"10.1155\/2014\/582849","article-title":"Oxidative stresses and mitochondrial dysfunction in age-related hearing loss","volume":"2014","author":"Fujimoto","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.mad.2010.04.006","article-title":"Mitochondrial oxidative damage and apoptosis in age-related hearing loss","volume":"131","author":"Someya","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2174\/1874609811003010020","article-title":"Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys","volume":"3","author":"Someya","year":"2010","journal-title":"Curr. Aging Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19432","DOI":"10.1073\/pnas.0908786106","article-title":"Age-related hearing loss in C57BL\/6J mice is mediated by Bak-dependent mitochondrial apoptosis","volume":"106","author":"Someya","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.cell.2010.10.002","article-title":"Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction","volume":"143","author":"Someya","year":"2010","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1089\/ars.2011.4037","article-title":"Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea","volume":"16","author":"Menardo","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1044\/1059-0889.0503.11","article-title":"Sensorineural hearing loss and dyslipidemia","volume":"5","author":"Campbell","year":"1996","journal-title":"Am. J. Audiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.18632\/aging.101971","article-title":"Age-related hearing loss accelerates cerebrospinal fluid tau levels and brain atrophy: A longitudinal study","volume":"11","author":"Xu","year":"2019","journal-title":"Aging"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kao, Y.-C., Ho, P.-C., Tu, Y.-K., Jou, I., and Tsai, K.-J. (2020). Lipids and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041505"},{"key":"ref_23","first-page":"619","article-title":"Sets of coregulated serum lipids are associated with Alzheimer\u2019s disease pathophysiology","volume":"11","author":"Barupal","year":"2019","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e21990","DOI":"10.1002\/syn.21990","article-title":"Alzheimer\u2019s disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration","volume":"71","author":"Espinosa","year":"2017","journal-title":"Synapse"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105828","DOI":"10.1155\/2015\/105828","article-title":"Inflammation and oxidative stress: The molecular connectivity between insulin resistance, obesity, and Alzheimer\u2019s disease","volume":"2015","author":"Verdile","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/WAD.0b013e31823b2728","article-title":"Cerebrospinal fluid cytokine dynamics differ between Alzheimer\u2019s Disease patients and elderly controls","volume":"26","author":"Llano","year":"2011","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"180263","DOI":"10.1038\/sdata.2018.263","article-title":"Generation and quality control of lipidomics data for the alzheimer\u2019s disease neuroimaging initiative cohort","volume":"5","author":"Barupal","year":"2018","journal-title":"Sci. Data"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1212\/WNL.34.7.939","article-title":"Clinical diagnosis of Alzheimer\u2019s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer\u2019s Disease","volume":"34","author":"McKhann","year":"1984","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1214\/07-AOAS101","article-title":"On testing the significance of sets of genes","volume":"1","author":"Efron","year":"2007","journal-title":"Ann. Appl. Stat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/AUD.0000000000000075","article-title":"Factors associated with the accuracy of subjective assessments of hearing impairment","volume":"36","author":"Kamil","year":"2015","journal-title":"Ear Hear."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.neurobiolaging.2013.08.001","article-title":"Evidence of altered phosphatidylcholine metabolism in Alzheimer\u2019s disease","volume":"35","author":"Whiley","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.bbalip.2010.05.013","article-title":"Phospholipase A2 and arachidonic acid in Alzheimer\u2019s disease","volume":"1801","author":"Mucke","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1001\/archneur.63.11.1545","article-title":"Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: The Framingham Heart Study","volume":"63","author":"Schaefer","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_35","first-page":"226","article-title":"Inferior prefrontal cortex mediates the relationship between phosphatidylcholine and executive functions in healthy, older adults","volume":"8","author":"Zamroziewicz","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1067\/mhn.2002.127627","article-title":"Influence of lecithin on mitochondrial DNA and age-related hearing loss","volume":"127","author":"Seidman","year":"2002","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: Current state","volume":"15","author":"Kurutas","year":"2015","journal-title":"Nutr. J."},{"key":"ref_38","first-page":"1","article-title":"The role of mitochondrial oxidative stress in hearing loss","volume":"1","year":"2017","journal-title":"Neurol. Disord. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1001\/archotol.1996.01890230067013","article-title":"Age-related differences in cochlear microcirculation and auditory brain stem response","volume":"122","author":"Seidman","year":"1996","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fendo.2017.00060","article-title":"Lipid processing in the brain: A key regulator of systemic metabolism","volume":"8","author":"Bruce","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/S0022-2275(20)31629-1","article-title":"Delivery and turnover of plasma-derived essential PUFAs in mammalian brain","volume":"42","author":"Rapoport","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fnagi.2015.00003","article-title":"Targeting cholesterol homeostasis to fight hearing loss: A new perspective","volume":"7","author":"Malgrange","year":"2015","journal-title":"Front. Aging Neurosci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/12\/2556\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:38:54Z","timestamp":1760179134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/12\/2556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,28]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["cells9122556"],"URL":"https:\/\/doi.org\/10.3390\/cells9122556","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.15.252452","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,28]]}}}