Franzmeier N, Dewenter A, Frontzkowski L, Dichgans M, Rubinski A, Neitzel J, et al. Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer’s disease. Sci Adv. 2020;6. https://doi.org/10.1126/sciadv.abd1327.

Vogel JW, Young AL, Oxtoby NP, Smith R, Ossenkoppele R, Strandberg OT, et al. Four distinct trajectories of tau deposition identified in Alzheimer’s disease. Nature Med. 2021;27:871–81. https://doi.org/10.1038/s41591-021-01309-6.

Article  PubMed  CAS  Google Scholar 

Franzmeier N, Brendel M, Beyer L, Slemann L, Kovacs GG, Arzberger T, et al. Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat Commun. 2022;13:1362. https://doi.org/10.1038/s41467-022-28896-3.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nature Cell Bio. 2009;11:909–13. https://doi.org/10.1038/ncb1901.

Article  CAS  Google Scholar 

Mudher A, Colin M, Dujardin S, Medina M, Dewachter I, Alavi Naini SM, et al. What is the evidence that tau pathology spreads through prion-like propagation? Acta Neuropathol Commun. 2017;5:99. https://doi.org/10.1186/s40478-017-0488-7.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Braak H, Del Tredici K. Spreading of Tau Pathology in Sporadic Alzheimer’s Disease Along Cortico-cortical Top-Down Connections. Cereb Cortex. 2018;28:3372–84. https://doi.org/10.1093/cercor/bhy152.

Article  PubMed  PubMed Central  Google Scholar 

Rubinski A, Franzmeier N, Dewenter A, Luan Y, Smith R, Strandberg O, et al. Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease. Alzheimers Res Ther. 2022;14:139. https://doi.org/10.1186/s13195-022-01074-9.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sjobeck M, Haglund M, Englund E. White matter mapping in Alzheimer’s disease: a neuropathological study. Neurobiol Aging. 2006;27:673–80. https://doi.org/10.1016/j.neurobiolaging.2005.03.007.

Article  PubMed  Google Scholar 

Zhan X, Jickling GC, Ander BP, Liu D, Stamova B, Cox C, et al. Myelin injury and degraded myelin vesicles in Alzheimer’s disease. Curr Alzheimer Res. 2014;11:232–8. https://doi.org/10.2174/1567205011666140131120922.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Couttas TA, Kain N, Suchowerska AK, Quek LE, Turner N, Fath T, et al. Loss of ceramide synthase 2 activity, necessary for myelin biosynthesis, precedes tau pathology in the cortical pathogenesis of Alzheimer’s disease. Neurobiol Aging. 2016;43:89–100. https://doi.org/10.1016/j.neurobiolaging.2016.03.027.

Article  PubMed  CAS  Google Scholar 

Bouhrara M, Reiter DA, Bergeron CM, Zukley LM, Ferrucci L, Resnick SM, et al. Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content. Alzheimers Dement. 2018;14:998–1004. https://doi.org/10.1016/j.jalz.2018.03.007.

Article  PubMed  PubMed Central  Google Scholar 

Dean DC 3rd, Hurley SA, Kecskemeti SR, O’Grady JP, Canda C, Davenport-Sis NJ, et al. Association of amyloid pathology with myelin alteration in preclinical Alzheimer disease. JAMA Neurology. 2017;74:41–9. https://doi.org/10.1001/jamaneurol.2016.3232.

Article  PubMed  PubMed Central  Google Scholar 

Moscoso A, Silva-Rodríguez J, Aldrey JM, Cortés J, Pías-Peleteiro JM, Ruibal Á, et al. (18)F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum. Eur J Nucl Med Mol Imaging. 2022;49:1242–53. https://doi.org/10.1007/s00259-021-05493-y.

Article  PubMed  CAS  Google Scholar 

Desai MK, Mastrangelo MA, Ryan DA, Sudol KL, Narrow WC, Bowers WJ. Early oligodendrocyte/myelin pathology in Alzheimer’s disease mice constitutes a novel therapeutic target. Am J Pathol. 2010;177:1422–35. https://doi.org/10.2353/ajpath.2010.100087.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Desai MK, Sudol KL, Janelsins MC, Mastrangelo MA, Frazer ME, Bowers WJ. Triple-transgenic Alzheimer’s disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology. Glia. 2009;57:54–65. https://doi.org/10.1002/glia.20734.

Article  PubMed  PubMed Central  Google Scholar 

Nasrabady SE, Rizvi B, Goldman JE, Brickman AM. White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta Neuropathol Commun. 2018;6:22. https://doi.org/10.1186/s40478-018-0515-3.

Article  PubMed  PubMed Central  CAS  Google Scholar 

De Strooper B, Karran E. The Cellular Phase of Alzheimer’s Disease. Cell. 2016;164:603–15. https://doi.org/10.1016/j.cell.2015.12.056.

Article  PubMed  CAS  Google Scholar 

Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, et al. The Alzheimer’s disease neuroimaging initiative 3: continued innovation for clinical trial improvement. Alzheimers Dement. 2017;13:561–71. https://doi.org/10.1016/j.jalz.2016.10.006.

Article  PubMed  Google Scholar 

Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305:275–83. https://doi.org/10.1001/jama.2010.2008.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Auvity S, Tonietto M, Caille F, Bodini B, Bottlaender M, Tournier N, et al. Repurposing radiotracers for myelin imaging: a study comparing 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol,11C-MeDAS, and 11C-PiB. Eur J Nucl Med Mol Imaging. 2020;47:490–501. https://doi.org/10.1007/s00259-019-04516-z.

Article  PubMed  CAS  Google Scholar 

Bajaj A, LaPlante NE, Cotero VE, Fish KM, Bjerke RM, Siclovan T, et al. Identification of the protein target of myelin-binding ligands by immunohistochemistry and biochemical analyses. J Histochem Cytochem. 2013;61:19–30. https://doi.org/10.1369/0022155412467353.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Veronese M, Rizzo G, Belzunce M, Schubert J, Searle G, Whittington A, et al. Reproducibility of findings in modern PET neuroimaging: insight from the NRM2018 grand challenge. J Cereb Blood Flow Metab. 2021;41:2778–96. https://doi.org/10.1177/0271678X211015101.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921–3.

Article  PubMed  CAS  Google Scholar 

Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet. 2007;39:17–23. https://doi.org/10.1038/ng1934.

Article  PubMed  CAS  Google Scholar 

Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988;240:622–30. https://doi.org/10.1126/science.3283935.

Article  PubMed  CAS  Google Scholar 

Saher G, Stumpf SK. Cholesterol in myelin biogenesis and hypomyelinating disorders. Biochim Biophys Acta. 2015;1851:1083–94. https://doi.org/10.1016/j.bbalip.2015.02.010.

Article  PubMed  CAS  Google Scholar 

Blanchard JW, Akay LA, Davila-Velderrain J, von Maydell D, Mathys H, Davidson SM, et al. APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature. 2022;611:769–79. https://doi.org/10.1038/s41586-022-05439-w.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bartzokis G, Lu PH, Geschwind DH, Tingus K, Huang D, Mendez MF, et al. Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline into dementia. Biol Psychiatry. 2007;62:1380–7. https://doi.org/10.1016/j.biopsych.2007.03.024.

Article  PubMed  CAS  Google Scholar 

Operto G, Molinuevo JL, Cacciaglia R, Falcon C, Brugulat-Serrat A, Suarez-Calvet M, et al. Interactive effect of age and APOE-epsilon4 allele load on white matter myelin content in cognitively normal middle-aged subjects. NeuroImage Clin. 2019;24:101983. https://doi.org/10.1016/j.nicl.2019.101983.

Article  PubMed  PubMed Central  Google Scholar 

Koutsodendris N, Blumenfeld J, Agrawal A, Traglia M, Grone B, Zilberter M, et al. Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits. Nature Aging. 2023. https://doi.org/10.1038/s43587-023-00368-3.

Article  PubMed  PubMed Central  Google Scholar 

Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313:1939–49. https://doi.org/10.1001/jama.2015.4669.

Article  PubMed  PubMed Central  Google Scholar 

Salvado G, Grothe MJ, Groot C, Moscoso A, Scholl M, Gispert JD, et al. Differential associations of APOE-epsilon2 and APOE-epsilon4 alleles with PET-measured amyloid-beta and tau deposition in older individuals without dementia. Eur J Nucl Med Mol Imaging. 2021;48:2212–24. https://doi.org/10.1007/s00259-021-05192-8.

Article  PubMed