{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:27:01Z","timestamp":1792196821915,"version":"4.4.0"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"national institute on aging","doi-asserted-by":"publisher","award":["U01AG046152"],"award-info":[{"award-number":["U01AG046152"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"national institute on aging","doi-asserted-by":"publisher","award":["U01AG061356"],"award-info":[{"award-number":["U01AG061356"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"national institute on aging","doi-asserted-by":"publisher","award":["P30AG010161"],"award-info":[{"award-number":["P30AG010161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"national institute on aging","doi-asserted-by":"publisher","award":["R01AG015819"],"award-info":[{"award-number":["R01AG015819"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"national institute on aging","doi-asserted-by":"publisher","award":["R01AG017917"],"award-info":[{"award-number":["R01AG017917"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurodegeneration"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer\u2019s disease (AD). Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA mutation burden have both been associated with neurodegenerative diseases and cognitive decline. This study aims to systematically identify which common brain pathologies in the aged human brain are associated with mitochondrial recalibrations and to disentangle the relationship between these pathologies, mtDNAcn, mtDNA heteroplasmy, aging, neuronal loss, and cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole-genome sequencing data from\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u20091361 human brain samples from 5 different regions were used to quantify mtDNAcn as well as heteroplasmic mtDNA point mutations and small indels. Brain samples were assessed for 10 common pathologies. Annual cognitive test results were used to assess cognitive function proximal to death. For a subset of samples, neuronal proportions were estimated from RNA-seq profiles, and mass spectrometry was used to quantify the mitochondrial protein content of the tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>mtDNAcn was 7\u201314% lower in AD relative to control participants. When accounting for all 10 common neuropathologies, only tau was significantly associated with lower mtDNAcn in the dorsolateral prefrontal cortex. In the posterior cingulate cortex, TDP-43 pathology demonstrated a distinct association with mtDNAcn. No changes were observed in the cerebellum, which is affected late by pathologies. Neither age nor gender was associated with mtDNAcn in the studied brain regions when adjusting for pathologies. Mitochondrial content and mtDNAcn independently explained variance in cognitive function unaccounted by pathologies, implicating complex mitochondrial recalibrations in cognitive decline. In contrast, mtDNA heteroplasmy levels increased by 1.5% per year of life in the cortical regions, but displayed no association with any of the pathologies or cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We studied mtDNA quantity and quality in relation to mixed pathologies of aging and showed that tau and not amyloid-\u03b2 is primarily associated with reduced mtDNAcn. In the posterior cingulate cortex, the association of TDP-43 with low mtDNAcn points to a vulnerability of this region in limbic-predominant age-related TDP-43 encephalopathy. While we found low mtDNAcn in brain regions affected by pathologies, the absence of associations with mtDNA heteroplasmy burden indicates that mtDNA point mutations and small indels are unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-021-00495-8","type":"journal-article","created":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T14:02:26Z","timestamp":1636207346000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer\u2019s disease brain"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-9428","authenticated-orcid":false,"given":"Hans-Ulrich","family":"Klein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Trumpff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Sik","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie J.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Picard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"De Jager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,6]]},"reference":[{"issue":"6","key":"495_CR1","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","volume":"148","author":"J Nunnari","year":"2012","unstructured":"Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148(6):1145\u201359 https:\/\/doi.org\/10.1016\/j.cell.2012.02.035.","journal-title":"Cell."},{"issue":"7","key":"495_CR2","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","volume":"20","author":"JB Spinelli","year":"2018","unstructured":"Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20(7):745\u201354 https:\/\/doi.org\/10.1038\/s41556-018-0124-1.","journal-title":"Nat Cell Biol"},{"issue":"5","key":"495_CR3","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","volume":"61","author":"N Sun","year":"2016","unstructured":"Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell. 2016;61(5):654\u201366 https:\/\/doi.org\/10.1016\/j.molcel.2016.01.028.","journal-title":"Mol Cell"},{"issue":"1","key":"495_CR4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1172\/JCI120848","volume":"129","author":"E Area-Gomez","year":"2019","unstructured":"Area-Gomez E, Guardia-Laguarta C, Schon EA, Przedborski S. Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas. J Clin Invest. 2019;129(1):34\u201345 https:\/\/doi.org\/10.1172\/JCI120848.","journal-title":"J Clin Invest"},{"issue":"8","key":"495_CR5","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/1873-3468.14021","volume":"595","author":"R Filograna","year":"2020","unstructured":"Filograna R, Mennuni M, Alsina D, Larsson NG. Mitochondrial DNA copy number in human disease: the more the better? FEBS Lett. 2020. https:\/\/doi.org\/10.1002\/1873-3468.14021;595(8):976\u20131002.","journal-title":"FEBS Lett"},{"key":"495_CR6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.mito.2014.10.005","volume":"20","author":"AM D'Erchia","year":"2015","unstructured":"D'Erchia AM, Atlante A, Gadaleta G, Pavesi G, Chiara M, De Virgilio C, et al. Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity. Mitochondrion. 2015;20:13\u201321 https:\/\/doi.org\/10.1016\/j.mito.2014.10.005.","journal-title":"Mitochondrion."},{"issue":"2","key":"495_CR7","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41576-020-00284-x","volume":"22","author":"JB Stewart","year":"2021","unstructured":"Stewart JB, Chinnery PF. Extreme heterogeneity of human mitochondrial DNA from organelles to populations. Nat Rev Genet. 2021;22(2):106\u201318 https:\/\/doi.org\/10.1038\/s41576-020-00284-x.","journal-title":"Nat Rev Genet"},{"issue":"29","key":"495_CR8","doi-asserted-by":"publisher","first-page":"10726","DOI":"10.1073\/pnas.0403649101","volume":"101","author":"PE Coskun","year":"2004","unstructured":"Coskun PE, Beal MF, Wallace DC. Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci U S A. 2004;101(29):10726\u201331 https:\/\/doi.org\/10.1073\/pnas.0403649101.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"495_CR9","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s40478-016-0404-6","volume":"5","author":"W Wei","year":"2017","unstructured":"Wei W, Keogh MJ, Wilson I, Coxhead J, Ryan S, Rollinson S, et al. Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains. Acta Neuropathol Commun. 2017;5(1):13 https:\/\/doi.org\/10.1186\/s40478-016-0404-6.","journal-title":"Acta Neuropathol Commun."},{"issue":"2","key":"495_CR10","doi-asserted-by":"publisher","first-page":"319","DOI":"10.3233\/JAD-131715","volume":"40","author":"AC Rice","year":"2014","unstructured":"Rice AC, Keeney PM, Algarzae NK, Ladd AC, Thomas RR, Bennett JP Jr. Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer's disease hippocampi. J Alzheimers Dis. 2014;40(2):319\u201330 https:\/\/doi.org\/10.3233\/JAD-131715.","journal-title":"J Alzheimers Dis"},{"issue":"4","key":"495_CR11","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/sj.ejhg.5200629","volume":"9","author":"B Rodriguez-Santiago","year":"2001","unstructured":"Rodriguez-Santiago B, Casademont J, Nunes V. Is mitochondrial DNA depletion involved in Alzheimer's disease? Eur J Hum Genet. 2001;9(4):279\u201385 https:\/\/doi.org\/10.1038\/sj.ejhg.5200629.","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"495_CR12","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1101\/gr.269381.120","volume":"31","author":"SY Yang","year":"2021","unstructured":"Yang SY, Castellani CA, Longchamps RJ, Pillalamarri VK, O'Rourke B, Guallar E, et al. Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease. Genome Res. 2021;31(3):349\u201358 https:\/\/doi.org\/10.1101\/gr.269381.120.","journal-title":"Genome Res"},{"issue":"11","key":"495_CR13","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.mad.2005.06.008","volume":"126","author":"T Frahm","year":"2005","unstructured":"Frahm T, Mohamed SA, Bruse P, Gemund C, Oehmichen M, Meissner C. Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart. Mech Ageing Dev. 2005;126(11):1192\u2013200 https:\/\/doi.org\/10.1016\/j.mad.2005.06.008.","journal-title":"Mech Ageing Dev"},{"key":"495_CR14","doi-asserted-by":"publisher","unstructured":"Miller FJ, Rosenfeldt FL, Zhang C, Linnane AW, Nagley P. Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res 2003;31(11):e61. https:\/\/doi.org\/10.1093\/nar\/gng060, 61e, 661.","DOI":"10.1093\/nar\/gng060"},{"issue":"3","key":"495_CR15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005939","volume":"12","author":"M Wachsmuth","year":"2016","unstructured":"Wachsmuth M, Hubner A, Li M, Madea B, Stoneking M. Age-related and Heteroplasmy-related variation in human mtDNA copy number. PLoS Genet. 2016;12(3):e1005939 https:\/\/doi.org\/10.1371\/journal.pgen.1005939.","journal-title":"PLoS Genet"},{"issue":"1","key":"495_CR16","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1146\/annurev-biochem-060408-093701","volume":"79","author":"NG Larsson","year":"2010","unstructured":"Larsson NG. Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem. 2010;79(1):683\u2013706. https:\/\/doi.org\/10.1146\/annurev-biochem-060408-093701.","journal-title":"Annu Rev Biochem"},{"issue":"5","key":"495_CR17","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/ng1769","volume":"38","author":"A Bender","year":"2006","unstructured":"Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet. 2006;38(5):515\u20137 https:\/\/doi.org\/10.1038\/ng1769.","journal-title":"Nat Genet"},{"issue":"2","key":"495_CR18","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1006\/geno.1994.1525","volume":"23","author":"M Corral-Debrinski","year":"1994","unstructured":"Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, McKee AC, Beal MF, et al. Marked changes in mitochondrial DNA deletion levels in Alzheimer brains. Genomics. 1994;23(2):471\u20136 https:\/\/doi.org\/10.1006\/geno.1994.1525.","journal-title":"Genomics."},{"issue":"s1","key":"495_CR19","doi-asserted-by":"publisher","first-page":"S161","DOI":"10.3233\/JAD-179939","volume":"64","author":"DA Bennett","year":"2018","unstructured":"Bennett DA, Buchman AS, Boyle PA, Barnes LL, Wilson RS, Schneider JA. Religious orders study and rush memory and aging project. J Alzheimers Dis. 2018;64(s1):S161\u2013S89 https:\/\/doi.org\/10.3233\/JAD-179939.","journal-title":"J Alzheimers Dis"},{"issue":"24","key":"495_CR20","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1212\/01.wnl.0000271090.28148.24","volume":"69","author":"JA Schneider","year":"2007","unstructured":"Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197\u2013204 https:\/\/doi.org\/10.1212\/01.wnl.0000271090.28148.24.","journal-title":"Neurology."},{"issue":"3","key":"495_CR21","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1001\/archneur.61.3.378","volume":"61","author":"DA Bennett","year":"2004","unstructured":"Bennett DA, Schneider JA, Wilson RS, Bienias JL, Arnold SE. Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch Neurol. 2004;61(3):378\u201384 https:\/\/doi.org\/10.1001\/archneur.61.3.378.","journal-title":"Arch Neurol"},{"issue":"5","key":"495_CR22","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S1474-4422(06)70417-3","volume":"5","author":"DA Bennett","year":"2006","unstructured":"Bennett DA, Schneider JA, Tang Y, Arnold SE, Wilson RS. The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol. 2006;5(5):406\u201312 https:\/\/doi.org\/10.1016\/S1474-4422(06)70417-3.","journal-title":"Lancet Neurol"},{"issue":"7","key":"495_CR23","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1212\/WNL.0000000000003610","volume":"88","author":"S Nag","year":"2017","unstructured":"Nag S, Yu L, Wilson RS, Chen EY, Bennett DA, Schneider JA. TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD. Neurology. 2017;88(7):653\u201360 https:\/\/doi.org\/10.1212\/WNL.0000000000003610.","journal-title":"Neurology."},{"issue":"Pt 10","key":"495_CR24","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1093\/brain\/aws234","volume":"135","author":"JA Schneider","year":"2012","unstructured":"Schneider JA, Arvanitakis Z, Yu L, Boyle PA, Leurgans SE, Bennett DA. Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain. 2012;135(Pt 10):3005\u201314 https:\/\/doi.org\/10.1093\/brain\/aws234.","journal-title":"Brain."},{"issue":"1","key":"495_CR25","first-page":"19","volume":"3","author":"S Love","year":"2014","unstructured":"Love S, Chalmers K, Ince P, Esiri M, Attems J, Jellinger K, et al. Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue. Am J Neurodegener Dis. 2014;3(1):19\u201332.","journal-title":"Am J Neurodegener Dis"},{"issue":"22","key":"495_CR26","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1212\/WNL.0000000000002175","volume":"85","author":"PA Boyle","year":"2015","unstructured":"Boyle PA, Yu L, Nag S, Leurgans S, Wilson RS, Bennett DA, et al. Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons. Neurology. 2015;85(22):1930\u20136 https:\/\/doi.org\/10.1212\/WNL.0000000000002175.","journal-title":"Neurology."},{"issue":"1","key":"495_CR27","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/bpa.12365","volume":"27","author":"Z Arvanitakis","year":"2017","unstructured":"Arvanitakis Z, Capuano AW, Leurgans SE, Buchman AS, Bennett DA, Schneider JA. The relationship of cerebral vessel pathology to brain microinfarcts. Brain Pathol. 2017;27(1):77\u201385 https:\/\/doi.org\/10.1111\/bpa.12365.","journal-title":"Brain Pathol"},{"issue":"11","key":"495_CR28","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.1161\/STROKEAHA.111.623462","volume":"42","author":"AS Buchman","year":"2011","unstructured":"Buchman AS, Leurgans SE, Nag S, Bennett DA, Schneider JA. Cerebrovascular disease pathology and parkinsonian signs in old age. Stroke. 2011;42(11):3183\u20139 https:\/\/doi.org\/10.1161\/STROKEAHA.111.623462.","journal-title":"Stroke."},{"issue":"3","key":"495_CR29","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1161\/STROKEAHA.110.595082","volume":"42","author":"Z Arvanitakis","year":"2011","unstructured":"Arvanitakis Z, Leurgans SE, Barnes LL, Bennett DA, Schneider JA. Microinfarct pathology, dementia, and cognitive systems. Stroke. 2011;42(3):722\u20137 https:\/\/doi.org\/10.1161\/STROKEAHA.110.595082.","journal-title":"Stroke."},{"issue":"6","key":"495_CR30","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1002\/ana.24388","volume":"77","author":"S Nag","year":"2015","unstructured":"Nag S, Yu L, Capuano AW, Wilson RS, Leurgans SE, Bennett DA, et al. Hippocampal sclerosis and TDP-43 pathology in aging and Alzheimer disease. Ann Neurol. 2015;77(6):942\u201352 https:\/\/doi.org\/10.1002\/ana.24388.","journal-title":"Ann Neurol"},{"issue":"1","key":"495_CR31","doi-asserted-by":"publisher","first-page":"160089","DOI":"10.1038\/sdata.2016.89","volume":"3","author":"M Allen","year":"2016","unstructured":"Allen M, Carrasquillo MM, Funk C, Heavner BD, Zou F, Younkin CS, et al. Human whole genome genotype and transcriptome data for Alzheimer's and other neurodegenerative diseases. Sci Data. 2016;3(1):160089. https:\/\/doi.org\/10.1038\/sdata.2016.89.","journal-title":"Sci Data"},{"issue":"1","key":"495_CR32","doi-asserted-by":"publisher","first-page":"180185","DOI":"10.1038\/sdata.2018.185","volume":"5","author":"M Wang","year":"2018","unstructured":"Wang M, Beckmann ND, Roussos P, Wang E, Zhou X, Wang Q, et al. The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer's disease. Sci Data. 2018;5(1):180185. https:\/\/doi.org\/10.1038\/sdata.2018.185.","journal-title":"Sci Data."},{"issue":"1","key":"495_CR33","doi-asserted-by":"publisher","first-page":"180142","DOI":"10.1038\/sdata.2018.142","volume":"5","author":"PL De Jager","year":"2018","unstructured":"De Jager PL, Ma Y, McCabe C, Xu J, Vardarajan BN, Felsky D, et al. A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research. Sci Data. 2018;5(1):180142. https:\/\/doi.org\/10.1038\/sdata.2018.142.","journal-title":"Sci Data."},{"issue":"1","key":"495_CR34","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/1471-2105-14-89","volume":"14","author":"Y Zhong","year":"2013","unstructured":"Zhong Y, Wan YW, Pang K, Chow LM, Liu Z. Digital sorting of complex tissues for cell type-specific gene expression profiles. BMC Bioinformatics. 2013;14(1):89. https:\/\/doi.org\/10.1186\/1471-2105-14-89.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"495_CR35","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13024-020-00392-6","volume":"15","author":"X Wang","year":"2020","unstructured":"Wang X, Allen M, Li S, Quicksall ZS, Patel TA, Carnwath TP, et al. Deciphering cellular transcriptional alterations in Alzheimer's disease brains. Mol Neurodegener. 2020;15(1):38 https:\/\/doi.org\/10.1186\/s13024-020-00392-6.","journal-title":"Mol Neurodegener"},{"issue":"6","key":"495_CR36","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41593-020-0635-5","volume":"23","author":"AP Wingo","year":"2020","unstructured":"Wingo AP, Fan W, Duong DM, Gerasimov ES, Dammer EB, Liu Y, et al. Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain. Nat Neurosci. 2020;23(6):696\u2013700 https:\/\/doi.org\/10.1038\/s41593-020-0635-5.","journal-title":"Nat Neurosci"},{"key":"495_CR37","doi-asserted-by":"publisher","unstructured":"Thul PJ, Akesson L, Wiking M, Mahdessian D, Geladaki A, Ait Blal H, et al. A subcellular map of the human proteome. Science. 2017;356(6340) https:\/\/doi.org\/10.1126\/science.aal3321.","DOI":"10.1126\/science.aal3321"},{"issue":"1","key":"495_CR38","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1214\/10-STS321","volume":"25","author":"K Imai","year":"2010","unstructured":"Imai K, Keele L, Yamamoto T. Identification, inference and sensitivity analysis for causal mediation effects. Stat Sci. 2010;25(1):51\u201371. https:\/\/doi.org\/10.1214\/10-STS321.","journal-title":"Stat Sci"},{"issue":"1","key":"495_CR39","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3758\/s13428-017-0862-1","volume":"50","author":"S Epskamp","year":"2018","unstructured":"Epskamp S, Borsboom D, Fried EI. Estimating psychological networks and their accuracy: a tutorial paper. Behav Res Methods. 2018;50(1):195\u2013212 https:\/\/doi.org\/10.3758\/s13428-017-0862-1.","journal-title":"Behav Res Methods"},{"issue":"7","key":"495_CR40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005306","volume":"11","author":"J Ding","year":"2015","unstructured":"Ding J, Sidore C, Butler TJ, Wing MK, Qian Y, Meirelles O, et al. Assessing mitochondrial DNA variation and copy number in lymphocytes of ~2,000 Sardinians using tailored sequencing analysis tools. PLoS Genet. 2015;11(7):e1005306 https:\/\/doi.org\/10.1371\/journal.pgen.1005306.","journal-title":"PLoS Genet"},{"issue":"1","key":"495_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228166","volume":"15","author":"RJ Longchamps","year":"2020","unstructured":"Longchamps RJ, Castellani CA, Yang SY, Newcomb CE, Sumpter JA, Lane J, et al. Evaluation of mitochondrial DNA copy number estimation techniques. PLoS One. 2020;15(1):e0228166 https:\/\/doi.org\/10.1371\/journal.pone.0228166.","journal-title":"PLoS One"},{"issue":"4","key":"495_CR42","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.mito.2009.03.003","volume":"9","author":"W Guo","year":"2009","unstructured":"Guo W, Jiang L, Bhasin S, Khan SM, Swerdlow RH. DNA extraction procedures meaningfully influence qPCR-based mtDNA copy number determination. Mitochondrion. 2009;9(4):261\u20135 https:\/\/doi.org\/10.1016\/j.mito.2009.03.003.","journal-title":"Mitochondrion."},{"issue":"7","key":"495_CR43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180467","volume":"12","author":"E Nacheva","year":"2017","unstructured":"Nacheva E, Mokretar K, Soenmez A, Pittman AM, Grace C, Valli R, et al. DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation. PLoS One. 2017;12(7):e0180467 https:\/\/doi.org\/10.1371\/journal.pone.0180467.","journal-title":"PLoS One"},{"issue":"3","key":"495_CR44","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/alzrt254","volume":"6","author":"ME Murray","year":"2014","unstructured":"Murray ME, Dickson DW. Is pathological aging a successful resistance against amyloid-beta or preclinical Alzheimer's disease? Alzheimers Res Ther. 2014;6(3):24 https:\/\/doi.org\/10.1186\/alzrt254.","journal-title":"Alzheimers Res Ther"},{"issue":"23","key":"495_CR45","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","volume":"22","author":"W Wang","year":"2013","unstructured":"Wang W, Li L, Lin WL, Dickson DW, Petrucelli L, Zhang T, et al. The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons. Hum Mol Genet. 2013;22(23):4706\u201319 https:\/\/doi.org\/10.1093\/hmg\/ddt319.","journal-title":"Hum Mol Genet"},{"issue":"8","key":"495_CR46","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/nm.4130","volume":"22","author":"W Wang","year":"2016","unstructured":"Wang W, Wang L, Lu J, Siedlak SL, Fujioka H, Liang J, et al. The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Nat Med. 2016;22(8):869\u201378 https:\/\/doi.org\/10.1038\/nm.4130.","journal-title":"Nat Med"},{"issue":"3","key":"495_CR47","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","volume":"183","author":"CH Yu","year":"2020","unstructured":"Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, et al. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS\/STING in ALS. Cell. 2020;183(3):636\u201349 e18. https:\/\/doi.org\/10.1016\/j.cell.2020.09.020.","journal-title":"Cell."},{"issue":"6","key":"495_CR48","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1093\/brain\/awz099","volume":"142","author":"PT Nelson","year":"2019","unstructured":"Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142(6):1503\u201327 https:\/\/doi.org\/10.1093\/brain\/awz099.","journal-title":"Brain."},{"issue":"4","key":"495_CR49","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1093\/brain\/awy049","volume":"141","author":"H Botha","year":"2018","unstructured":"Botha H, Mantyh WG, Murray ME, Knopman DS, Przybelski SA, Wiste HJ, et al. FDG-PET in tau-negative amnestic dementia resembles that of autopsy-proven hippocampal sclerosis. Brain. 2018;141(4):1201\u201317 https:\/\/doi.org\/10.1093\/brain\/awy049.","journal-title":"Brain."},{"issue":"4","key":"495_CR50","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s00401-016-1537-1","volume":"131","author":"KA Josephs","year":"2016","unstructured":"Josephs KA, Murray ME, Whitwell JL, Tosakulwong N, Weigand SD, Petrucelli L, et al. Updated TDP-43 in Alzheimer's disease staging scheme. Acta Neuropathol. 2016;131(4):571\u201385 https:\/\/doi.org\/10.1007\/s00401-016-1537-1.","journal-title":"Acta Neuropathol"},{"issue":"1","key":"495_CR51","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s40478-018-0531-3","volume":"6","author":"S Nag","year":"2018","unstructured":"Nag S, Yu L, Boyle PA, Leurgans SE, Bennett DA, Schneider JA. TDP-43 pathology in anterior temporal pole cortex in aging and Alzheimer's disease. Acta Neuropathol Commun. 2018;6(1):33 https:\/\/doi.org\/10.1186\/s40478-018-0531-3.","journal-title":"Acta Neuropathol Commun"},{"key":"495_CR52","doi-asserted-by":"publisher","unstructured":"Longchamps R, Yang S, Castellani C, Shi W, Lane J, Grove M, et al. Genome-wide analysis of mitochondrial DNA copy number reveals multiple loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation. bioRxiv. 2021;2021.01.25.428086. https:\/\/doi.org\/10.1101\/2021.01.25.428086.","DOI":"10.1101\/2021.01.25.428086"},{"issue":"6","key":"495_CR53","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1007\/s00439-020-02249-w","volume":"140","author":"S Hagg","year":"2020","unstructured":"Hagg S, Jylhava J, Wang Y, Czene K, Grassmann F. Deciphering the genetic and epidemiological landscape of mitochondrial DNA abundance. Hum Genet. 2020. https:\/\/doi.org\/10.1007\/s00439-020-02249-w;140(6):849\u201361.","journal-title":"Hum Genet"},{"key":"495_CR54","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.mito.2020.03.001","volume":"52","author":"HB Shim","year":"2020","unstructured":"Shim HB, Arshad O, Gadawska I, Cote HCF, Hsieh AYY. Platelet mtDNA content and leukocyte count influence whole blood mtDNA content. Mitochondrion. 2020;52:108\u201314 https:\/\/doi.org\/10.1016\/j.mito.2020.03.001.","journal-title":"Mitochondrion."},{"key":"495_CR55","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.freeradbiomed.2016.06.031","volume":"100","author":"DA Bota","year":"2016","unstructured":"Bota DA, Davies KJ. Mitochondrial Lon protease in human disease and aging: including an etiologic classification of Lon-related diseases and disorders. Free Radic Biol Med. 2016;100:188\u201398 https:\/\/doi.org\/10.1016\/j.freeradbiomed.2016.06.031.","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"495_CR56","doi-asserted-by":"publisher","first-page":"4277","DOI":"10.1038\/s41598-020-61142-8","volume":"10","author":"E Area-Gomez","year":"2020","unstructured":"Area-Gomez E, Larrea D, Pera M, Agrawal RR, Guilfoyle DN, Pirhaji L, et al. APOE4 is associated with differential regional vulnerability to bioenergetic deficits in aged APOE mice. Sci Rep. 2020;10(1):4277 https:\/\/doi.org\/10.1038\/s41598-020-61142-8.","journal-title":"Sci Rep"},{"issue":"23","key":"495_CR57","doi-asserted-by":"publisher","first-page":"e2404","DOI":"10.1212\/WNL.0000000000009582","volume":"94","author":"J Yin","year":"2020","unstructured":"Yin J, Reiman EM, Beach TG, Serrano GE, Sabbagh MN, Nielsen M, et al. Effect of ApoE isoforms on mitochondria in Alzheimer disease. Neurology. 2020;94(23):e2404\u2013e11 https:\/\/doi.org\/10.1212\/WNL.0000000000009582.","journal-title":"Neurology."},{"issue":"10","key":"495_CR58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013513","volume":"5","author":"A Brinckmann","year":"2010","unstructured":"Brinckmann A, Weiss C, Wilbert F, von Moers A, Zwirner A, Stoltenburg-Didinger G, et al. Regionalized pathology correlates with augmentation of mtDNA copy numbers in a patient with myoclonic epilepsy with ragged-red fibers (MERRF-syndrome). PLoS One. 2010;5(10):e13513 https:\/\/doi.org\/10.1371\/journal.pone.0013513.","journal-title":"PLoS One"},{"issue":"14","key":"495_CR59","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1113\/jphysiol.2012.230185","volume":"590","author":"S Larsen","year":"2012","unstructured":"Larsen S, Nielsen J, Hansen CN, Nielsen LB, Wibrand F, Stride N, et al. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol. 2012;590(14):3349\u201360 https:\/\/doi.org\/10.1113\/jphysiol.2012.230185.","journal-title":"J Physiol"},{"issue":"8","key":"495_CR60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008120","volume":"16","author":"E Patrick","year":"2020","unstructured":"Patrick E, Taga M, Ergun A, Ng B, Casazza W, Cimpean M, et al. Deconvolving the contributions of cell-type heterogeneity on cortical gene expression. PLoS Comput Biol. 2020;16(8):e1008120 https:\/\/doi.org\/10.1371\/journal.pcbi.1008120.","journal-title":"PLoS Comput Biol"},{"issue":"4","key":"495_CR61","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1016\/j.ajpath.2011.07.004","volume":"179","author":"KJ Kopeikina","year":"2011","unstructured":"Kopeikina KJ, Carlson GA, Pitstick R, Ludvigson AE, Peters A, Luebke JI, et al. Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse model of tauopathy and in human Alzheimer's disease brain. Am J Pathol. 2011;179(4):2071\u201382 https:\/\/doi.org\/10.1016\/j.ajpath.2011.07.004.","journal-title":"Am J Pathol"},{"issue":"7","key":"495_CR62","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1523\/JNEUROSCI.5927-11.2012","volume":"32","author":"K Shahpasand","year":"2012","unstructured":"Shahpasand K, Uemura I, Saito T, Asano T, Hata K, Shibata K, et al. Regulation of mitochondrial transport and inter-microtubule spacing by tau phosphorylation at the sites hyperphosphorylated in Alzheimer's disease. J Neurosci. 2012;32(7):2430\u201341 https:\/\/doi.org\/10.1523\/JNEUROSCI.5927-11.2012.","journal-title":"J Neurosci"},{"issue":"1","key":"495_CR63","doi-asserted-by":"publisher","first-page":"24756","DOI":"10.1038\/srep24756","volume":"6","author":"XC Li","year":"2016","unstructured":"Li XC, Hu Y, Wang ZH, Luo Y, Zhang Y, Liu XP, et al. Human wild-type full-length tau accumulation disrupts mitochondrial dynamics and the functions via increasing mitofusins. Sci Rep. 2016;6(1):24756. https:\/\/doi.org\/10.1038\/srep24756.","journal-title":"Sci Rep"},{"issue":"22","key":"495_CR64","doi-asserted-by":"publisher","first-page":"4881","DOI":"10.1093\/hmg\/ddw312","volume":"25","author":"R Kandimalla","year":"2016","unstructured":"Kandimalla R, Manczak M, Fry D, Suneetha Y, Sesaki H, Reddy PH. Reduced dynamin-related protein 1 protects against phosphorylated tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer's disease. Hum Mol Genet. 2016;25(22):4881\u201397 https:\/\/doi.org\/10.1093\/hmg\/ddw312.","journal-title":"Hum Mol Genet"},{"issue":"1","key":"495_CR65","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3233\/JAD-200286","volume":"77","author":"IW Weidling","year":"2020","unstructured":"Weidling IW, Wilkins HM, Koppel SJ, Hutfles L, Wang X, Kalani A, et al. Mitochondrial DNA manipulations affect tau oligomerization. J Alzheimers Dis. 2020;77(1):149\u201363 https:\/\/doi.org\/10.3233\/JAD-200286.","journal-title":"J Alzheimers Dis"},{"issue":"35","key":"495_CR66","doi-asserted-by":"publisher","first-page":"9057","DOI":"10.1523\/JNEUROSCI.1469-06.2006","volume":"26","author":"L Devi","year":"2006","unstructured":"Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J Neurosci. 2006;26(35):9057\u201368 https:\/\/doi.org\/10.1523\/JNEUROSCI.1469-06.2006.","journal-title":"J Neurosci"},{"issue":"10","key":"495_CR67","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/nm.1868","volume":"14","author":"H Du","year":"2008","unstructured":"Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med. 2008;14(10):1097\u2013105 https:\/\/doi.org\/10.1038\/nm.1868.","journal-title":"Nat Med"},{"issue":"1","key":"495_CR68","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00401-020-02234-7","volume":"141","author":"L Vaillant-Beuchot","year":"2021","unstructured":"Vaillant-Beuchot L, Mary A, Pardossi-Piquard R, Bourgeois A, Lauritzen I, Eysert F, et al. Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer's disease models and human brains. Acta Neuropathol. 2021;141(1):39\u201365 https:\/\/doi.org\/10.1007\/s00401-020-02234-7.","journal-title":"Acta Neuropathol"},{"issue":"12","key":"495_CR69","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41398-017-0048-8","volume":"7","author":"GR Fries","year":"2017","unstructured":"Fries GR, Bauer IE, Scaini G, Wu MJ, Kazimi IF, Valvassori SS, et al. Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder. Transl Psychiatry. 2017;7(12):1283 https:\/\/doi.org\/10.1038\/s41398-017-0048-8.","journal-title":"Transl Psychiatry"},{"issue":"9","key":"495_CR70","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1007\/s00439-014-1458-9","volume":"133","author":"J Mengel-From","year":"2014","unstructured":"Mengel-From J, Thinggaard M, Dalgard C, Kyvik KO, Christensen K, Christiansen L. Mitochondrial DNA Copy number in peripheral blood cells declines with age and is associated with general health among elderly. Hum Genet. 2014;133(9):1149\u201359 https:\/\/doi.org\/10.1007\/s00439-014-1458-9.","journal-title":"Hum Genet"},{"key":"495_CR71","doi-asserted-by":"publisher","unstructured":"Rausser S, Trumpff C, McGill MA, Junker A, Wang W, Ho S, et al. Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures. bioRxiv. 2021:2020.10.16.342923. https:\/\/doi.org\/10.1101\/2020.10.16.342923.","DOI":"10.1101\/2020.10.16.342923"},{"key":"495_CR72","doi-asserted-by":"publisher","unstructured":"Moore AZ, Ding J, Tuke MA, Wood AR, Bandinelli S, Frayling TM, et al. Influence of cell distribution and diabetes status on the association between mitochondrial DNA copy number and aging phenotypes in the InCHIANTI study. Aging Cell. 2018;17(1) https:\/\/doi.org\/10.1111\/acel.12683.","DOI":"10.1111\/acel.12683"},{"key":"495_CR73","doi-asserted-by":"publisher","unstructured":"Pyle A, Anugrha H, Kurzawa-Akanbi M, Yarnall A, Burn D, Hudson G. Reduced mitochondrial DNA copy number is a biomarker of Parkinson's disease. Neurobiol Aging. 2016;38:216 e7- e10. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2015.10.033.","DOI":"10.1016\/j.neurobiolaging.2015.10.033"},{"issue":"2","key":"495_CR74","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","volume":"9","author":"CC Liu","year":"2013","unstructured":"Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106\u201318 https:\/\/doi.org\/10.1038\/nrneurol.2012.263.","journal-title":"Nat Rev Neurol"},{"issue":"6","key":"495_CR75","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.molmed.2010.04.004","volume":"16","author":"Y Huang","year":"2010","unstructured":"Huang Y. Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease. Trends Mol Med. 2010;16(6):287\u201394 https:\/\/doi.org\/10.1016\/j.molmed.2010.04.004.","journal-title":"Trends Mol Med"},{"issue":"8","key":"495_CR76","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1073\/pnas.1419651112","volume":"112","author":"M Li","year":"2015","unstructured":"Li M, Schroder R, Ni S, Madea B, Stoneking M. Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations. Proc Natl Acad Sci U S A. 2015;112(8):2491\u20136 https:\/\/doi.org\/10.1073\/pnas.1419651112.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"495_CR77","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1186\/s12864-017-4287-0","volume":"18","author":"R Zhang","year":"2017","unstructured":"Zhang R, Wang Y, Ye K, Picard M, Gu Z. Independent impacts of aging on mitochondrial DNA quantity and quality in humans. BMC Genomics. 2017;18(1):890 https:\/\/doi.org\/10.1186\/s12864-017-4287-0.","journal-title":"BMC Genomics"},{"issue":"2","key":"495_CR78","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/hmg\/11.2.133","volume":"11","author":"MT Lin","year":"2002","unstructured":"Lin MT, Simon DK, Ahn CH, Kim LM, Beal MF. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. Hum Mol Genet. 2002;11(2):133\u201345 https:\/\/doi.org\/10.1093\/hmg\/11.2.133.","journal-title":"Hum Mol Genet"},{"issue":"11","key":"495_CR79","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/j.bbabio.2015.05.015","volume":"1847","author":"MJ Keogh","year":"2015","unstructured":"Keogh MJ, Chinnery PF. Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta. 2015;1847(11):1401\u201311 https:\/\/doi.org\/10.1016\/j.bbabio.2015.05.015.","journal-title":"Biochim Biophys Acta"},{"issue":"Pt 3","key":"495_CR80","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1042\/BJ20021594","volume":"370","author":"R Rossignol","year":"2003","unstructured":"Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T. Mitochondrial threshold effects. Biochem J. 2003;370(Pt 3):751\u201362 https:\/\/doi.org\/10.1042\/BJ20021594.","journal-title":"Biochem J"}],"container-title":["Molecular Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-021-00495-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13024-021-00495-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-021-00495-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T14:03:31Z","timestamp":1636207411000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularneurodegeneration.biomedcentral.com\/articles\/10.1186\/s13024-021-00495-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,6]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["495"],"URL":"https:\/\/doi.org\/10.1186\/s13024-021-00495-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.741125616.793590120","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.05.20.21257456","asserted-by":"object"}]},"ISSN":["1750-1326"],"issn-type":[{"value":"1750-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,6]]},"assertion":[{"value":"2 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ROS and MAP studies were approved by the Institutional Review Board of Rush University Medical Center. All participants signed an informed consent, an Anatomic Gift Act for brain donation, and a repository consent to allow their data and biospecimens to be shared. The Mayo case-control study was approved by the Mayo Clinic Institutional Review Board. The MSBB study was approved by the Mount Sinai and JJ Peters VA Medical Center Institutional Review Boards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"75"}}