Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease
Open accessAbstract
OBJECTIVE: To identify a novel biochemical marker that precedes clinical symptoms in Alzheimer disease (AD). METHODS: Using quantitative polymerase chain reaction techniques, we measured circulating cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) from study participants, selected from a cohort of 282 subjects, who were classified according to their concentrations of amyloid β1-42, total tau, and phosphorylated tau and by the presence or absence of dementia, into asymptomatic subjects at risk of AD, symptomatic patients diagnosed with sporadic AD, presymptomatic subjects carrying pathogenic PSEN1 mutations, and patients diagnosed with frontotemporal lobar degeneration (FTLD). We performed equivalent studies in a separate validation cohort of sporadic AD and FTLD patients. In addition, we measured mtDNA copy number in cultured cortical neurons from mutant amyloid precursor protein/presenilin1 (APP/PS1) transgenic mice. RESULTS: Asymptomatic patients at risk of AD and symptomatic AD patients, but not FTLD patients, exhibit a significant decrease in circulating cell-free mtDNA in the CSF. These observations were confirmed in the validation cohort. In addition, presymptomatic subjects carrying pathogenic PSEN1 gene mutations show low mtDNA content in CSF before the appearance of AD-related biomarkers in CSF. Moreover, mtDNA content in CSF discriminates with high sensitivity and specificity AD patients from either controls or patients with FTLD. Furthermore, cultured cortical neurons from APP/PS1 transgenic mice have fewer mtDNA copies before the appearance of altered synaptic markers. INTERPRETATION: Low content of mtDNA in CSF may be a novel biomarker for the early detection of preclinical AD. These findings support the hypothesis that mtDNA depletion is a characteristic pathophysiological factor of neurodegeneration in AD.
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For many subjects with suspected AD or increased risk, what are currently considered downstream biomarker changes potentially precede upstream biomarker changes.
“Our hypothesis, therefore, can accommodate a growing realization that for many subjects with suspected AD, or who have an increased risk of developing AD, what are currently considered downstream biomarker changes potentially precede upstream biomarker changes [206-213].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [213]
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McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments
Bustin, S. A., Benes, V., Garson, J. A., Hellemans, J., Huggett, J., Kubista, M., Mueller, R., Nolan, T., Pfaffl, M. W., Shipley, G. L., et al. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2008.112797 · Cited by 16,303 · see citing works
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155 · see citing works
Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria
Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P. H., Albert, M., et al. (1998) · Neurology · doi:10.1212/wnl.51.6.1546 · Cited by 5,047 · see citing works
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · see citing works
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078 · see citing works
Neuropathology of older persons without cognitive impairment from two community-based studies
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., & Wilson, R. S. (2006) · Neurology · doi:10.1212/01.wnl.0000219668.47116.e6 · Cited by 1,336 · see citing works
Fagan, A. M., Mintun, M. A., Mach, R. H., Lee, S., Dence, C. S., Shah, A. R., LaRossa, G. N., Spinner, M. L., Klunk, W. E., Mathis, C. A., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20730 · Cited by 1,246 · see citing works
Tapiola, T., Alafuzoff, I., Herukka, S.-K., Parkkinen, L., Hartikainen, P., Soininen, H., & Pirttilä, T. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.596 · Cited by 896 · see citing works
CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study
Strozyk, D., Blennow, K., White, L. R., & Launer, L. J. (2003) · Neurology · doi:10.1212/01.wnl.0000046581.81650.d0 · Cited by 604 · see citing works
The Alzheimer’s Disease Mitochondrial Cascade Hypothesis
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100339 · Cited by 562 · cited 2× · see citing works
“Converging evidence indicates that AD is associated with alterations in bioenergetics and mitochondrial function.(13,14) Neurons are highly dependent on aerobic energy provided by mitochondria, which contain several copies of their own DNA (mtDNA).”
BackgroundImpaired Mitochondrial Biogenesis Contributes to Mitochondrial Dysfunction in Alzheimer's Disease
Sheng, B., Wang, X.-L., Su, B., Lee, H.-G., Casadesus, G., Perry, G., & Zhu, X.-W. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07581.x · Cited by 538 · see citing works
Presenilins Are Enriched in Endoplasmic Reticulum Membranes Associated with Mitochondria
Área-Gómez, E., de Groof, A. J. C., Boldogh, I. R., Bird, T. D., Gibson, G. E., Koehler, C. M., Yu, W. H., Duff, K., Yaffe, M. P., Pon, L. A., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090219 · Cited by 397 · see citing works
Clark, C. M., Xie, S., Chittams, J., Ewbank, D., Peskind, E., Galasko, D., Morris, J. C., McKeel, D. W., Farlow, M., Weitlauf, S. L., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.12.1696 · Cited by 357 · see citing works
A mitochondrial etiology of Alzheimer and Parkinson disease
Coskun, P. E., Wyrembak, J., Schriner, S. E., Chen, H.-W., Marciniack, C., LaFerla, F. M., & Wallace, D. C. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.008 · Cited by 297 · see citing works
CSF biomarkers in frontotemporal lobar degeneration with known pathology
Bian, H., Van Swieten, J. C., Leight, S., Massimo, L., Wood, E., Forman, M., Moore, P., de Koning, I., Clark, C. M., Rosso, S., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000311445.21321.fc · Cited by 216 · see citing works
DNA extraction procedures meaningfully influence qPCR-based mtDNA copy number determination
Guo, W., Jiang, L., Bhasin, S., Khan, S. M., & Swerdlow, R. H. (2009) · Mitochondrion · doi:10.1016/j.mito.2009.03.003 · Cited by 183 · see citing works
Coskun, P. E., Wyrembak, J., Derbereva, O., Melkonian, G., Doran, E. W., Lott, I. T., Head, E., Cotman, C. W., & Wallace, D. C. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100351 · Cited by 158 · see citing works
The QPCR assay for analysis of mitochondrial DNA damage, repair, and relative copy number
Hunter, S. E., Jung, D., Giulio, R. T. D., & Meyer, J. N. (2010) · Methods · doi:10.1016/j.ymeth.2010.01.033 · Cited by 157 · see citing works
Hertze, J., Minthon, L., Zetterberg, H., Vanmechelen, E., Blennow, K., & Hansson, O. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100207 · Cited by 132 · see citing works
Bioenergetic Origins of Complexity and DiseasePreprint
Wallace, D. C. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010462 · Cited by 125 · see citing works
Pavlov, P. F., Wiehager, B., Sakai, J., Frykman, S., Behbahani, H., Winblad, B. G., & Ankarcrona, M. (2010) · The FASEB Journal · doi:10.1096/fj.10-157230 · Cited by 113 · see citing works
CSF biomarkers in neurodegenerative diseases
Mattsson, N. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.082 · Cited by 74 · see citing works
Predictors of Preclinical Alzheimer Disease and Dementia: A Clinicopathologic Study
Galvin, J. E., Powlishta, K. K., Wilkins, K., McKeel, D. W., Xiong, C., Grant, E., Storandt, M., & Morris, J. C. (2005) · Archives of Neurology · doi:10.1001/archneur.62.5.758 · Cited by 2 · see citing works
Flagged first, then by citations
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Sorted by citations
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Mitochondrial DNA copy number in human disease: the more the better?
Filograna, R., Mennuni, M., Alsina, D., & Larsson, N. (2020) · FEBS Letters · doi:10.1002/1873-3468.14021 · Cited by 478 · see citing works
Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01926-1 · Cited by 378 · see citing works
Biological aging processes underlying cognitive decline and neurodegenerative disease
Gonzales, M. M., Garbarino, V. R., Pollet, E., Palavicini, J. P., Kellogg, D. L., Kraig, E., & Orr, M. E. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158453 · Cited by 394 · see citing works
A key role for MAM in mediating mitochondrial dysfunction in Alzheimer disease
Area-Gomez, E., de Groof, A., Bonilla, E., Montesinos, J., Tanji, K., Boldogh, I., Pon, L., & Schon, E. A. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0215-0 · Cited by 235 · see citing works
D'Erchia, A. M., Atlante, A., Gadaleta, G., Pavesi, G., Chiara, M., De Virgilio, C., Manzari, C., Mastropasqua, F., Prazzoli, G. M., Picardi, E., et al. (2015) · Mitochondrion · doi:10.1016/j.mito.2014.10.005 · Cited by 197 · see citing works
Multiplexed Target Detection Using DNA-Binding Dye Chemistry in Droplet Digital PCR
McDermott, G. P., Do, D., Litterst, C. M., Maar, D., Hindson, C. M., Steenblock, E. R., Legler, T. C., Jouvenot, Y., Marrs, S. H., Bemis, A., et al. (2013) · Analytical Chemistry · doi:10.1021/ac403061n · Cited by 191 · see citing works
Epigenetics of Alzheimer’s Disease
Perković, M. N., Paska, A. V., Konjevod, M., Kouter, K., Štrac, D. Š., Erjavec, G. N., & Pivac, N. (2021) · Biomolecules · doi:10.3390/biom11020195 · Cited by 181 · see citing works
Digital PCR analysis of circulating nucleic acids
Hudecova, I. (2015) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2015.03.015 · Cited by 178 · see citing works
Targeting mitophagy in neurodegenerative diseases
Antico, O., Thompson, P. W., Hertz, N. T., Muqit, M. M. K., & Parton, L. E. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01105-0 · Cited by 178 · see citing works
Bae, J. H., Jo, S. I., Kim, S. J., Lee, J. M., Jeong, J. H., Kang, J. S., Cho, N., Kim, S. S., Lee, E. Y., & Moon, J. (2019) · Cells · doi:10.3390/cells8040328 · Cited by 162 · see citing works
ccf-mtDNA as a Potential Link Between the Brain and Immune System in Neuro-Immunological Disorders
Gambardella, S., Limanaqi, F., Ferese, R., Biagioni, F., Campopiano, R., Centonze, D., & Fornai, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01064 · Cited by 141 · see citing works
Mastroeni, D., Khdour, O. M., Delvaux, E., Nolz, J., Olsen, G., Berchtold, N. C., Cotman, C. W., Hecht, S. M., & Coleman, P. D. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.09.003 · Cited by 131 · see citing works
Reduced cerebrospinal fluid mitochondrial DNA is a biomarker for early‐stage Parkinson's disease
Pyle, A., Brennan, R. R., Kurzawa‐Akanbi, M., Yarnall, A. J., Thouin, A., Mollenhauer, B., Burn, D. J., Chinnery, P. F., & Hudson, G. (2015) · Annals of Neurology · doi:10.1002/ana.24515 · Cited by 121 · see citing works
O'Hara, R., Tedone, E., Ludlow, A., Huang, E., Arosio, B., Mari, D., & Shay, J. W. (2019) · Genome Research · doi:10.1101/gr.250480.119 · Cited by 121 · see citing works
Rice, A. C., Keeney, P. M., Algarzae, N. K., Ladd, A. C., Thomas, R. R., & Bennett, J. P. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131715 · Cited by 117 · see citing works
Zhao, Y., Liu, B., Xu, L., Yu, S., Fu, J., Wang, J., Yan, X., & Su, J. (2021) · Antioxidants · doi:10.3390/antiox10121917 · Cited by 114 · see citing works
Avila-Muñoz, E., & Arias, C. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.004 · Cited by 114 · see citing works
Kageyama, Y., Kasahara, T., Kato, M., Sakai, S., Deguchi, Y., Tani, M., Kuroda, K., Hattori, K., Yoshida, S., Goto, Y., et al. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.06.001 · Cited by 112 · see citing works
Gaetani, L., Paoletti, F. P., Bellomo, G., Mancini, A., Simoni, S., Filippo, M. D., & Parnetti, L. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.09.011 · Cited by 108 · see citing works
Peng, Y., Gao, P., Shi, L., Chen, L., Liu, J., & Long, J. (2020) · Antioxidants & Redox Signaling · doi:10.1089/ars.2019.7763 · Cited by 110 · see citing works
Chaudhry, S. R., Hafez, A., Jahromi, B. R., Kinfe, T. M., Lamprecht, A., Niemela, M. R., & Muhammad, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072035 · Cited by 103 · see citing works
Hoekstra, J. G., Hipp, M. J., Montine, T. J., & Kennedy, S. R. (2016) · Annals of Neurology · doi:10.1002/ana.24709 · Cited by 105 · see citing works
Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration
Wilkins, H. M., Weidling, I. W., Ji, Y., & Swerdlow, R. H. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00508 · Cited by 102 · see citing works
Quan, S., Fu, X., Cai, H., Ren, Z., Xu, Y., & Jia, L. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00815-2 · Cited by 107 · see citing works
Halilovic, A., Schmedt, T., Benischke, A., Hamill, C. E., Chen, Y., Santos, J. H., & Jurkunas, U. V. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6532 · Cited by 96 · see citing works
Cerebrospinal Fluid Mitochondrial DNA
Walko, T. D., Bola, R. A., Hong, J. D., Au, A. K., Bell, M. J., Kochanek, P. M., Clark, R. S. B., & Aneja, R. K. (2014) · Shock · doi:10.1097/shk.0000000000000160 · Cited by 93 · see citing works
Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment
Lowes, H., Pyle, A., Santibanez‐Koref, M., & Hudson, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00362-y · Cited by 92 · see citing works
Moya, G. E., Rivera, P. D., & Dittenhafer‐Reed, K. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137030 · Cited by 88 · see citing works
Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease
Khoonsari, P. E., Månberg, A., Lönnberg, M., Mikus, M. S., Kilander, L., Lannfelt, L., Bergquist, J., Ingelsson, M., Nilsson, P., Kultima, K., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150672 · Cited by 84 · see citing works
Clark, I. A., & Vissel, B. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13181 · Cited by 84 · see citing works
Expanding and validating the biomarkers for mitochondrial diseases
Maresca, A., Dotto, V. D., Romagnoli, M., Morgia, C. L., Vito, L. D., Capristo, M., Valentino, M. L., Carelli, V., & the ER-MITO Study Group (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01967-y · Cited by 77 · see citing works
Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges
Wu, C., Yang, L., Feng, S., Zhu, L., Yang, L., Liu, T. C., & Duan, R. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00216-8 · Cited by 71 · see citing works
Mitochondrial DNA signals driving immune responses: Why, How, Where?
Giordano, L., Ware, S. A., Lagranha, C. J., & Kaufman, B. A. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02042-0 · Cited by 77 · see citing works
Sang, S., Pan, X., Chen, Z., Zeng, F., Pan, S., Liu, H., Jin, L., Fei, G., Wang, C., Ren, S., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0354-2 · Cited by 69 · see citing works
Lopes, C., Mota, S., Deus, C., Tavares, H., & Beatriz, M. (2022) · Cells · doi:10.3390/cells11152364 · Cited by 71 · see citing works
Microglial toll-like receptors and Alzheimer’s disease
Su, F., Bai, F., Zhou, H., & Zhang, Z. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.10.010 · Cited by 67 · see citing works
Liang, J., Wang, C., Zhang, H., Huang, J., Xie, J., & Chen, N. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.755665 · Cited by 66 · see citing works
Mitochondrial DNA: Inherent Complexities Relevant to Genetic Analyses
Ferreira, T., & Rodrı́guez, S. (2024) · Genes · doi:10.3390/genes15050617 · Cited by 70 · see citing works
Reassessment of Pioglitazone for Alzheimer’s Disease
Saunders, A. M., Burns, D. K., & Gottschalk, W. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666958 · Cited by 67 · see citing works
Mambro, T. D., Pellielo, G., Agyapong, E. D., Carinci, M., Chianese, D., Giorgi, C., Morciano, G., Patergnani, S., Pinton, P., & Rimessi, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098181 · Cited by 65 · see citing works
Emerging perspectives on mitochondrial dysfunction and inflammation in Alzheimer’s disease
Yoo, S., Park, J., Kim, S., & Jung, Y. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.1.274 · Cited by 65 · see citing works
Xu, Y., Xu, L., Han, M., Liu, X., Li, F., Zhou, X., Wang, Y., & Bi, J. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.09.094 · Cited by 63 · see citing works
Varhaug, K. N., Vedeler, C. A., Myhr, K., Aarseth, J. H., Tzoulis, C., & Bindoff, L. A. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.12.003 · Cited by 63 · see citing works
Cilento, E. M., Jin, L., Stewart, T., Shi, M., Sheng, L., & Zhang, J. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14635 · Cited by 60 · see citing works
Yuzefovych, L. V., Pastukh, V. M., Ruchko, M. V., Simmons, J. D., Richards, W. O., & Rachek, L. I. (2019) · PLOS ONE · doi:10.1371/journal.pone.0222278 · Cited by 59 · see citing works
Potential biomarkers to follow the progression and treatment response of Huntington’s disease
Disatnik, M.-H., Joshi, A. U., Saw, N. L., Shamloo, M., Leavitt, B. R., Qi, X., & Mochly-Rosen, D. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20160776 · Cited by 58 · see citing works
Dixit, S., Fessel, J. P., & Harrison, F. E. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.08.021 · Cited by 58 · see citing works
Mitochondria and Alzheimer’s Disease: the Role of Mitochondrial Genetic Variation
Ridge, P. G., & Kauwe, J. S. K. (2018) · Current Genetic Medicine Reports · doi:10.1007/s40142-018-0132-2 · Cited by 57 · see citing works
Koklesová, L., Samec, M., Líšková, A., Zhai, K., Büsselberg, D., Giordano, F. A., Kubatka, P., & Golubnitschaja, O. (2021) · The EPMA Journal · doi:10.1007/s13167-021-00237-2 · Cited by 54 · see citing works
Mitochondrial links between brain aging and Alzheimer’s disease
Wilkins, H., & Swerdlow, R. H. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00261-2 · Cited by 53 · see citing works
Involvement of Mitochondria in Parkinson’s Disease
Choong, C., & Mochizuki, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242317027 · Cited by 55 · see citing works
Cell-free mitochondrial DNA in progressive multiple sclerosis
Lowes, H., Pyle, A., Duddy, M., & Hudson, G. (2018) · Mitochondrion · doi:10.1016/j.mito.2018.07.008 · Cited by 52 · see citing works
The Protective Mechanism of TFAM on Mitochondrial DNA and its Role in Neurodegenerative Diseases
Song, Y., Wang, W., Wang, B., & Shi, Q. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03841-7 · Cited by 51 · see citing works
Hajjo, R., Sabbah, D. A., Abusara, O. H., & Bawab, A. Q. A. (2022) · Diagnostics · doi:10.3390/diagnostics12122975 · Cited by 55 · see citing works
Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics
Liu, Y., Qing, H., & Deng, Y. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15057865 · Cited by 50 · see citing works
Kaur, P., Khera, A., Alajangi, H. K., Sharma, A., Jaiswal, P. K., Singh, G., & Barnwal, R. P. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03164-z · Cited by 53 · see citing works
Bioenergetic Dysfunction and Inflammation in Alzheimer’s Disease: A Possible Connection
Wilkins, H., Carl, S. M., Greenlief, A. C. S., Festoff, B. W., & Swerdlow, R. H. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00311 · Cited by 48 · see citing works
Rosa, H. S., Ajaz, S., Gnudi, L., & Malik, A. N. (2020) · The FASEB Journal · doi:10.1096/fj.202000959rr · Cited by 48 · see citing works
Droplet digital PCR technology promises new applications and research areas
Manoj, P. (2014) · Mitochondrial DNA Part A · doi:10.3109/19401736.2014.913168 · Cited by 48 · see citing works
Circulating Mitochondrial DNA is Linked to Progression and Prognosis of Epithelial Ovarian Cancer
Meng, X., Schwarzenbach, H., Yang, Y., Müller, V., Li, N., Tian, D., Shen, Y., & Gong, Z. (2019) · Translational Oncology · doi:10.1016/j.tranon.2019.05.015 · Cited by 48 · see citing works
Líšková, A., Samec, M., Koklesová, L., Kúdela, E., Kubatka, P., & Golubnitschaja, O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042007 · Cited by 48 · see citing works
Mitochondrial DNA and Exercise: Implications for Health and Injuries in Sports
Zanini, G., De Gaetano, A., Selleri, V., Savino, G., Cossarizza, A., Pinti, M., Mattioli, A. V., & Nasi, M. (2021) · Cells · doi:10.3390/cells10102575 · Cited by 46 · see citing works
Nidadavolu, L. S., Feger, D. M., Chen, D., Wu, Y., Grodstein, F., Gross, A. L., Bennett, D. A., Walston, J. D., Oh, E. S., & Abadir, P. M. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00342-y · Cited by 45 · see citing works
He, Y., Lu, X., Wu, H., Cai, W., Yang, L.-Q., Xu, L., Sun, H., & Kong, Q. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.01.015 · Cited by 46 · see citing works
Leurs, C. E., Podlesniy, P., Trullás, R., Balk, L. J., Steenwijk, M. D., Malekzadeh, A., Piehl, F., Uitdehaag, B. M. J., Killestein, J., van Horssen, J., et al. (2017) · Multiple Sclerosis Journal · doi:10.1177/1352458517699874 · Cited by 45 · see citing works
Self-citationCerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum
Cervera‐Carles, L., Alcolea, D. A., Estanga, A., Ecay‐Torres, M., Izagirre, A., Clerigué, M., García‐Sebastián, M., Villanúa, J., Escalas, C., Blesa, R., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.12.009 · Cited by 44 · see citing works
Self-citationFighting Parkinson’s disease: The return of the mitochondria
Zambrano, K., Barba, D., Castillo, K., Noboa, L. E., Argueta-Zamora, D., Robayo, P., Arizaga, E., Caicedo, A., & Gavilanes, A. W. D. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.02.003 · Cited by 44 · see citing works
Mitochondria dysfunction and bipolar disorder: From pathology to therapy
Lam, X.-J., Xu, B., Yeo, P. L., Cheah, P.-S., & Ling, K. (2023) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2023.04.002 · Cited by 44 · see citing works
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Galik-Olah, Z., Kalman, J. L., Tóth, M. E., Zvara, Á., Sántha, M., Ivitz, E., Janka, Z., & Pákáski, M. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-140141 · Cited by 43 · see citing works
The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases
Carvalho, C., Correia, S. C., Cardoso, S., Plácido, A. I., Candeias, E., Duarte, A. I., & Moreira, P. I. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1058160 · Cited by 43 · see citing works
Mitochondrial DAMPs: Key mediators in neuroinflammation and neurodegenerative disease pathogenesis
Yu, H., Ren, K., Jin, Y., Zhang, L., Liu, H., Huang, Z., Zhang, Z., Chen, X., Yang, Y., & Wei, Z. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110217 · Cited by 44 · see citing works
Accurate quantitation of circulating cell-free mitochondrial DNA in plasma by droplet digital PCR
Ye, W., Tang, X., Liu, C., Wen, C., Li, W., & Lyu, J. (2017) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-017-0217-x · Cited by 42 · see citing works
Xu, Y., Cheng, L. J., Sun, J., Li, F., Liu, X., Wei, Y., Han, M., Zhu, Z., Bi, J., Lai, C., et al. (2021) · Neurochemical Research · doi:10.1007/s11064-020-03192-y · Cited by 42 · see citing works
Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function
Zhang, Y., Liu, X., Wiggins, K. L., Kurniansyah, N., Guo, X., Rodrigue, A., Zhao, W., Yanek, L. R., Ratliff, S. M., Pitsillides, A., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207157 · Cited by 39 · see citing works
CSF biomarkers in neurodegenerative and vascular dementias
Llorens, F., Schmitz, M., Ferrer, I., & Zerr, I. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.03.003 · Cited by 39 · see citing works
The “mitochondrial stress responses”: the “Dr. Jekyll and Mr. Hyde” of neuronal disorders
Rimessi, A., Patergnani, S., Morciano, G., Carinci, M., Leo, S., & Pinton, P. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.339473 · Cited by 39 · see citing works
Pérez‐Santiago, J., Schrier, R. D., Oliveira, M. F., Gianella, S., Var, S. R., Day, T. R. C., Ramirez-Gaona, M., Suben, J. D., Murrell, B., Massanella, M., et al. (2015) · Journal of NeuroVirology · doi:10.1007/s13365-015-0384-5 · Cited by 39 · see citing works
Kichev, A., Eede, P., Gressèns, P., Thornton, C., & Hagberg, H. (2017) · Developmental Neuroscience · doi:10.1159/000464244 · Cited by 37 · see citing works
Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer’s Disease
Podlesniy, P., Llorens, F., Puigròs, M., Serra, N., Falla, D. S., Schmidt, C., Hermann, P., Zerr, I., & Trullás, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176298 · Cited by 38 · see citing works
Self-citationMishra, Y., Kumar, A., & Kaundal, R. K. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04412-0 · Cited by 37 · see citing works
Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C. elegans
Chakraborty, S., Chen, P., Bornhorst, J., Schwerdtle, T., Schumacher, F., Kleuser, B., Bowman, A. B., & Aschner, M. (2015) · Metallomics · doi:10.1039/c5mt00052a · Cited by 35 · see citing works
Mehta, S. R., Pérez‐Santiago, J., Hulgan, T., Day, T. R. C., Barnholtz‐Sloan, J. S., Gittleman, H. R., Letendre, S. L., Ellis, R. J., Heaton, R. K., Patton, S. M., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0848-z · Cited by 35 · see citing works
Caicedo, A., Zambrano, K., Sanon, S., & Gavilanes, A. W. D. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.02.006 · Cited by 34 · see citing works
Liu, X., Wang, W., Chen, H., Zhang, H., & Zhang, N.-X. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0239-3 · Cited by 33 · see citing works
Al‐Kafaji, G., Bakheit, H. F., Alharbi, M. A., Farahat, A. A., Jailani, M., Ebrahin, B. H., & Bakhiet, M. (2020) · NeuroMolecular Medicine · doi:10.1007/s12017-019-08588-w · Cited by 33 · see citing works
Boosting mitochondrial health to counteract neurodegeneration
Burtscher, J., Romani, M., Bernardo, G., Popa, T., Ziviani, E., Hummel, F. C., Sorrentino, V., & Millet, G. P. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102289 · Cited by 34 · see citing works
Immunomodulatory role of mitochondrial DAMPs: a missing link in pathology?
Garg, M., Johri, S., & Chakraborty, K. (2022) · FEBS Journal · doi:10.1111/febs.16563 · Cited by 32 · see citing works
Bellelli, F., Angioni, D., Arosio, B., Vellas, B. J., & Barreto, P. D. S. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102699 · Cited by 33 · see citing works
Nasi, M., Bianchini, E., Biasi, S. D., Gibellini, L., Neroni, A., Mattioli, M., Pinti, M., Iannone, A., Mattioli, A. V., Simone, A. M., et al. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.577107 · Cited by 31 · see citing works
Discontinued disease-modifying therapies for Alzheimer’s disease: status and future perspectives
Imbimbo, B. P., Lozupone, M., Watling, M., & Panza, F. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1795127 · Cited by 31 · see citing works
Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt‐Jakob disease
Podlesniy, P., Llorens, F., Golańska, E., Sikorska, B., Liberski, P. P., Zerr, I., & Trullás, R. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.12.011 · Cited by 31 · see citing works
Self-citationChaudhry, A., Houlden, H., & Rizig, M. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116886 · Cited by 30 · see citing works
Mitochondrial Disorders in Alzheimer’s Disease
Sukhorukov, V. S., Mudzhiri, N. M., Voronkova, A. S., Baranich, T. I., Glinkina, V. V., & Illarioshkin, S. N. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921060055 · Cited by 30 · see citing works
Intracellular DAMPs in Neurodegeneration and Their Role in Clinical Therapeutics
Kaur, J., Singh, H., & Naqvi, S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03289-9 · Cited by 30 · see citing works
Mitochondrial DNA ( mtDNA ) as fluid biomarker in neurodegenerative disorders: A systematic review
Risi, B., Imarisio, A., Cuconato, G., Padovani, A., Valente, E. M., & Filosto, M. (2025) · European Journal of Neurology · doi:10.1111/ene.70014 · Cited by 29 · see citing works
Cell-free DNA as a biomarker in stroke: Current status, problems and perspectives
Glebova, K. V., Вейко, Н. Н., Nikonov, A. A., Porokhovnik, L. N., & Kostuyk, S. V. (2018) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2017.1420032 · Cited by 29 · see citing works
Cerebrospinal fluid mitochondrial DNA in neuromyelitis optica spectrum disorder
Yamashita, K., Kinoshita, M., Miyamoto, K., Namba, A., Shimizu, M., Koda, T., Sugimoto, T., Mori, Y., Yoshioka, Y., Nakatsuji, Y., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1162-0 · Cited by 28 · see citing works
Marmolejo-Garza, A., Medeiros-Furquim, T., Rao, R. G., Eggen, B. J. L., Boddeke, E., & Dolga, A. M. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119326 · Cited by 28 · see citing works
Thiamine deficiency contributes to synapse and neural circuit defects
Yu, Q., Liu, H., Sang, S., Chen, L., Zhao, Y., Wang, Y., & Zhong, C. (2018) · Biological Research · doi:10.1186/s40659-018-0184-5 · Cited by 28 · see citing works
- Authors
- Podlesniy, P., Figueiro‐Silva, J., Llado, A., Antonell, A., Sanchez‐Valle, R., Alcolea, D., Lleo, A., Molinuevo, J. L., Serra, N., & Trullas, R.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Neurology Service Hospital Clinic de Barcelona Barcelona Spain
- Hospital Clínic de Barcelona (ES)
- Hospital de Sant Pau (ES)
- Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas, CIBERNED Madrid Spain
- Neurobiology Unit Instituto de Investigaciones Biomedicas de Barcelona, Consejo Superior de Investigaciones Cientificas, CSIC Barcelona Spain
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2013-09-04
- Volume
- 74
- Issue
- 5
- Pages
- 655-668
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W1778065122
- Cited by
- 219
- References
- 24
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 13 · 2023: 18 · 2022: 21 · 2021: 21 · 2020: 17 · 2019: 12 · 2018: 20 · 2017: 11 · 2016: 21 · 2015: 16 · 2014: 15 · 2013: 4
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Funders
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Alzheimer's disease, preclinical Alzheimer's disease, mitochondrial DNA, cerebrospinal fluid biomarkers, PSEN1 mutations, frontotemporal lobar degeneration, APP/PS1 mice, cortical neurons, mtDNA depletion, neurodegeneration, early detection
- MeSH terms
- Alzheimer Disease, Animals, DNA, Mitochondrial, Female, Humans, Male, Mice, Transgenic, Peptide Fragments, Phosphorylation, Biomarkers, Amyloid beta-Protein Precursor, tau Proteins, Mice, Presenilin-1, Cognitive Dysfunction, Prodromal Symptoms
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