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Feb, 2025;47 (1): 227-246.

Local molecular and connectomic contributions of tau-related neurodegeneration.

Fardin Nabizadeh, Alzheimer���s disease Neuroimaging Initiative (ADNI)
Author Information
  1. Fardin Nabizadeh: School of Medicine, Iran University of Medical Sciences, Tehran, Iran. fardinnabizade1378@gmail.com. ORCID
PMID: 39343862 DOI: 10.1007/s11357-024-01339-1

Abstract

neurodegeneration in Alzheimer's disease (AD) is known to be mostly driven by tau neurofibrillary tangles. However, both tau and neurodegeneration exhibit variability in their distribution across the brain and among individuals, and the relationship between tau and neurodegeneration might be influenced by several factors. I aimed to map local molecular and connectivity characteristics that affect the association between tau pathology and neurodegeneration. The current study was conducted on the cross-sectional tau-PET and longitudinal T1-weighted MRI scan data of 186 participants from the ADNI dataset including 71 cognitively unimpaired (CU) and 115 mild cognitive impairment (MCI) individuals. Furthermore, the normative molecular profile of a region was defined using neurotransmitter receptor densities, gene expression, T1w/T2w ratio (myelination), FDG-PET (glycolytic index, glucose metabolism, and oxygen metabolism), and synaptic density. I found that the excitatory-inhibitory (E:I) ratio, myelination, synaptic density, glycolytic index, and functional connectivity are linked with deviation in the relationship between tau and neurodegeneration. Furthermore, there was spatial similarity between tau pathology and glycolytic index, synaptic density, and functional connectivity across brain regions. The current study demonstrates that the regional susceptibility to tau-related neurodegeneration is associated with specific molecular and connectomic characteristics of the affected neural systems. I found that the molecular and connectivity architecture of the human brain is linked to the different effects of tau pathology on downstream neurodegeneration.

Keywords

Alzheimer���s disease Connectivity Mild cognitive impairment Molecular Neurodegeneration Tau

References

  1. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer���s disease. Alzheimers Dement. 2018;14(4):535���62. [PMID: 29653606]
  2. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer���s disease at 25 years. EMBO Mol Med. 2016;8(6):595���608. [PMID: 27025652]
  3. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Ch��telat G, Teunissen CE, et al. Alzheimer���s disease. The Lancet. 2021;397(10284):1577���90. [DOI: 10.1016/S0140-6736(20)32205-4]
  4. Das SR, Lyu X, Duong MT, Xie L, McCollum L, de Flores R, et al. Tau-atrophy variability reveals phenotypic heterogeneity in Alzheimer���s disease. Ann Neurol. 2021;90(5):751���62. [PMID: 34617306]
  5. Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer���s disease. Mol Neurodegener. 2020;15(1):40. [PMID: 32677986]
  6. Knopman DS, Lundt ES, Therneau TM, Vemuri P, Lowe VJ, Kantarci K, et al. Entorhinal cortex tau, amyloid-��, cortical thickness and memory performance in non-demented subjects. Brain. 2019;142(4):1148���60. [PMID: 30759182]
  7. Sch��ll M, Lockhart SN, Schonhaut DR, O���Neil JP, Janabi M, Ossenkoppele R, et al. PET imaging of Tau deposition in the aging human brain. Neuron. 2016;89(5):971���82. [PMID: 26938442]
  8. Das SR, Xie L, Wisse LEM, Ittyerah R, Tustison NJ, Dickerson BC, et al. Longitudinal and cross-sectional structural magnetic resonance imaging correlates of AV-1451 uptake. Neurobiol Aging. 2018;66:49���58. [PMID: 29518752]
  9. Otero-Garcia M, Mahajani SU, Wakhloo D, Tang W, Xue YQ, Morabito S, et al. Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer���s disease. Neuron. 2022;110(18):2929-48.e8. [PMID: 35882228]
  10. Lyu X, Duong MT, Xie L, de Flores R, Richardson H, Hwang G, et al. Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer���s continuum. Alzheimers Dement. 2024;20(3):1586���600. [PMID: 38050662]
  11. Zheng L, Rubinski A, Denecke J, Luan Y, Smith R, Strandberg O, et al. Combined connectomics, MAPT gene expression, and amyloid deposition to explain regional tau deposition in Alzheimer disease. Ann Neurol. 2024;95(2):274���87. [PMID: 37837382]
  12. Tracy TE, Madero-P��rez J, Swaney DL, Chang TS, Moritz M, Konrad C, et al. Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell. 2022;185(4):712-28.e14. [PMID: 35063084]
  13. Zhang X, Alshakhshir N, Zhao L. Glycolytic metabolism, brain resilience, and Alzheimer���s disease. Front Neurosci. 2021;15:662242. [PMID: 33994936]
  14. Latimer CS, Burke BT, Liachko NF, Currey HN, Kilgore MD, Gibbons LE, et al. Resistance and resilience to Alzheimer���s disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort. Acta Neuropathol Commun. 2019;7(1):91. [PMID: 31174609]
  15. Zalocusky KA, Najm R, Taubes AL, Hao Y, Yoon SY, Koutsodendris N, et al. Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer���s disease. Nat Neurosci. 2021;24(6):786���98. [PMID: 33958804]
  16. Shi Y, Andhey PS, Ising C, Wang K, Snipes LL, Boyer K, et al. Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms. Neuron. 2021;109(15):2413-26.e7. [PMID: 34157306]
  17. Duong MT, Das SR, Lyu X, Xie L, Richardson H, Xie SX, et al. Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer���s disease. Nat Commun. 2022;13(1):1495. [PMID: 35314672]
  18. Khan AF, Adewale Q, Baumeister TR, Carbonell F, Zilles K, Palomero-Gallagher N, et al. Personalized brain models identify neurotransmitter receptor changes in Alzheimer���s disease. Brain. 2022;145(5):1785���804. [PMID: 34605898]
  19. Negro D, Opazo P (2024) Cognitive resilience in Alzheimer���s disease: from large-scale brain networks to synapses. Brain Commun 6(1). https://doi.org/10.1093/braincomms/fcae050
  20. Buckner RL, Sepulcre J, Talukdar T, Krienen FM, Liu H, Hedden T, et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer���s disease. J Neurosci. 2009;29(6):1860���73. [PMID: 19211893]
  21. Landau S, Jagust W (2016) Flortaucipir (AV-1451) processing methods. Alzheimer���s Disease Neuroimaging Initiative
  22. Jack CR Jr, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, et al. The Alzheimer���s disease neuroimaging initiative (ADNI): MRI methods. J Magn Reson Imaging. 2008;27(4):685���91. [PMID: 18302232]
  23. Fischl B, Salat DH, van der Kouwe AJ, Makris N, S��gonne F, Quinn BT, et al. Sequence-independent segmentation of magnetic resonance images. Neuroimage. 2004;23(Suppl 1):S69-84. [PMID: 15501102]
  24. Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012;489(7416):391���9. [PMID: 22996553]
  25. Hansen JY, Markello RD, Vogel JW, Seidlitz J, Bzdok D, Misic B. Mapping gene transcription and neurocognition across human neocortex. Nat Hum Behav. 2021;5(9):1240���50. [PMID: 33767429]
  26. Hawrylycz M, Miller JA, Menon V, Feng D, Dolbeare T, Guillozet-Bongaarts AL, et al. Canonical genetic signatures of the adult human brain. Nat Neurosci. 2015;18(12):1832���44. [PMID: 26571460]
  27. Hansen JY, Shafiei G, Markello RD, Smart K, Cox SML, N��rgaard M, et al. Mapping neurotransmitter systems to the structural and functional organization of the human neocortex. Nat Neurosci. 2022;25(11):1569���81. [PMID: 36303070]
  28. Vaishnavi SN, Vlassenko AG, Rundle MM, Snyder AZ, Mintun MA, Raichle ME. Regional aerobic glycolysis in the human brain. Proc Natl Acad Sci U S A. 2010;107(41):17757���62. [PMID: 20837536]
  29. Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, et al. Kinetic evaluation and test-retest reproducibility of [(11)C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. J Cereb Blood Flow Metab. 2018;38(11):2041���52. [PMID: 28792356]
  30. Chen MK, Mecca AP, Naganawa M, Gallezot JD, Toyonaga T, Mondal J, et al. Comparison of [(11)C]UCB-J and [(18)F]FDG PET in Alzheimer���s disease: a tracer kinetic modeling study. J Cereb Blood Flow Metab. 2021;41(9):2395���409. [PMID: 33757318]
  31. O���Dell RS, Mecca AP, Chen MK, Naganawa M, Toyonaga T, Lu Y, et al. Association of A�� deposition and regional synaptic density in early Alzheimer���s disease: a PET imaging study with [(11)C]UCB-J. Alzheimers Res Ther. 2021;13(1):11. [PMID: 33402201]
  32. Smart K, Liu H, Matuskey D, Chen MK, Torres K, Nabulsi N, et al. Binding of the synaptic vesicle radiotracer [(11)C]UCB-J is unchanged during functional brain activation using a visual stimulation task. J Cereb Blood Flow Metab. 2021;41(5):1067���79. [PMID: 32757741]
  33. Weiss JJ, Calvi R, Naganawa M, Toyonaga T, Farhadian SF, Chintanaphol M, et al. Preliminary in vivo evidence of reduced synaptic density in human immunodeficiency virus (HIV) despite Antiretroviral therapy. Clin Infect Dis. 2021;73(8):1404���11. [PMID: 34050746]
  34. Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, et al. In vivo evidence of lower synaptic vesicle density in schizophrenia. Mol Psychiatry. 2021;26(12):7690���8. [PMID: 34135473]
  35. Finnema SJ, Toyonaga T, Detyniecki K, Chen MK, Dias M, Wang Q, et al. Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: a [(11) C]UCB-J positron emission tomography study. Epilepsia. 2020;61(10):2183���93. [PMID: 32944949]
  36. Bini J, Holden D, Fontaine K, Mulnix T, Lu Y, Matuskey D, et al. Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand (11)C-UCB-J. EJNMMI Res. 2020;10(1):83. [PMID: 32666239]
  37. Mecca AP, Chen MK, O���Dell RS, Naganawa M, Toyonaga T, Godek TA, et al. In vivo measurement of widespread synaptic loss in Alzheimer���s disease with SV2A PET. Alzheimers Dement. 2020;16(7):974���82. [PMID: 32400950]
  38. Finnema SJ, Rossano S, Naganawa M, Henry S, Gao H, Pracitto R, et al. A single-center, open-label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers. Epilepsia. 2019;60(5):958���67. [PMID: 30924924]
  39. Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, et al. Lower synaptic density is associated with depression severity and network alterations. Nat Commun. 2019;10(1):1529. [PMID: 30948709]
  40. Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, et al. Assessing synaptic density in Alzheimer disease with synaptic vesicle glycoprotein 2A positron emission tomographic imaging. JAMA Neurol. 2018;75(10):1215���24. [PMID: 30014145]
  41. Van Essen DC, Smith SM, Barch DM, Behrens TE, Yacoub E, Ugurbil K. The WU-Minn human connectome project: an overview. Neuroimage. 2013;80:62���79. [PMID: 23684880]
  42. Glasser MF, Sotiropoulos SN, Wilson JA, Coalson TS, Fischl B, Andersson JL, et al. The minimal preprocessing pipelines for the Human Connectome Project. Neuroimage. 2013;80:105���24. [PMID: 23668970]
  43. Cammoun L, Gigandet X, Meskaldji D, Thiran JP, Sporns O, Do KQ, et al. Mapping the human connectome at multiple scales with diffusion spectrum MRI. J Neurosci Methods. 2012;203(2):386���97. [PMID: 22001222]
  44. van der Weijden CWJ, Garc��a DV, Borra RJH, Thurner P, Meilof JF, van Laar PJ, et al. Myelin quantification with MRI: a systematic review of accuracy and reproducibility. Neuroimage. 2021;226:117561. [PMID: 33189927]
  45. Auvity S, Tonietto M, Caill�� 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(2):490���501. [PMID: 31686177]
  46. Zeydan B, Lowe VJ, Schwarz CG, Przybelski SA, Tosakulwong N, Zuk SM, et al. Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis. Mult Scler. 2018;24(6):739���49. [PMID: 28474977]
  47. Franzmeier N, Neitzel J, Rubinski A, Smith R, Strandberg O, Ossenkoppele R, et al. Functional brain architecture is associated with the rate of tau accumulation in Alzheimer���s disease. Nat Commun. 2020;11(1):347. [PMID: 31953405]
  48. Desikan RS, S��gonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31(3):968���80. [PMID: 16530430]
  49. Zheng L, Rubinski A, Denecke J, Luan Y, Smith R, Strandberg O, et al. Combined connectomics, MAPT gene expression, and amyloid deposition to explain regional tau deposition in Alzheimer disease. Ann Neurol. 2024;95(2):274���87. [PMID: 37837382]
  50. Carroll T, Guha S, Nehrke K, Johnson GVW. Tau post-translational modifications: potentiators of selective vulnerability in sporadic Alzheimer���s disease. Biology (Basel). 2021;10(10):1047. [PMID: 34681146]
  51. Leng K, Li E, Eser R, Piergies A, Sit R, Tan M, et al. Molecular characterization of selectively vulnerable neurons in Alzheimer���s disease. Nat Neurosci. 2021;24(2):276���87. [PMID: 33432193]
  52. Kiani L. Regional vulnerability to A�� and tau pathology. Nat Rev Neurol. 2024;20(3):133. [PMID: 38326399]
  53. Olajide OJ, Suvanto ME, Chapman CA (2021) Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer���s disease. Biol Open 10(1). https://doi.org/10.1242/bio.056796
  54. Yu M, Risacher SL, Nho KT, Wen Q, Oblak AL, Unverzagt FW, et al. Spatial transcriptomic patterns underlying amyloid-�� and tau pathology are associated with cognitive dysfunction in Alzheimer���s disease. Cell Rep. 2024;43(2):113691. [PMID: 38244198]
  55. Jack CR Jr, Wiste HJ, Schwarz CG, Lowe VJ, Senjem ML, Vemuri P, et al. Longitudinal tau PET in ageing and Alzheimer���s disease. Brain. 2018;141(5):1517���28. [PMID: 29538647]
  56. La Joie R, Visani AV, Baker SL, Brown JA, Bourakova V, Cha J et al (2020) Prospective longitudinal atrophy in Alzheimer���s disease correlates with the intensity and topography of baseline tau-PET. Sci Transl Med 12(524). https://doi.org/10.1126/scitranslmed.aau5732
  57. Jacobs HIL, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, et al. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci. 2018;21(3):424���31. [PMID: 29403032]
  58. Fornito A, Arnatkevi��i��t�� A, Fulcher BD. Bridging the gap between connectome and transcriptome. Trends Cogn Sci. 2019;23(1):34���50. [PMID: 30455082]
  59. Arnatkeviciute A, Markello RD, Fulcher BD, Misic B, Fornito A. Toward best practices for imaging transcriptomics of the human brain. Biol Psychiatry. 2023;93(5):391���404. [PMID: 36725139]
  60. Sepulcre J, Grothe MJ, d���Oleire Uquillas F, Ortiz-Ter��n L, Diez I, Yang HS, et al. Neurogenetic contributions to amyloid beta and tau spreading in the human cortex. Nat Med. 2018;24(12):1910���8. [PMID: 30374196]
  61. Montal V, Diez I, Kim CM, Orwig W, Bueichek�� E, Guti��rrez-Z����iga R, et al. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Sci Transl Med. 2022;14(655):eabn7273. [PMID: 35895837]
  62. Franzmeier N, Dewenter A, Frontzkowski L, Dichgans M, Rubinski A, Neitzel J et al (2020) Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer���s disease. Sci Adv 6(48). https://doi.org/10.1126/sciadv.abd1327
  63. Nabizadeh F (2023) Initiative ftAsdN. sTREM2 is associated with attenuated tau aggregate accumulation in the presence of amyloid-�� pathology. Brain Commun 5(6). https://doi.org/10.1093/braincomms/fcad286
  64. Wang J, Huang Q, Chen X, You Z, He K, Guo Q et al (2024) Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer���s disease. Mol Psychiatry. https://doi.org/10.1038/s41380-024-02501-z
  65. Wang M, Lu J, Zhang Y, Zhang Q, Wang L, Wu P, et al. Characterization of tau propagation pattern and cascading hypometabolism from functional connectivity in Alzheimer���s disease. Hum Brain Mapp. 2024;45(7):e26689. [PMID: 38703095]
  66. Iaccarino L, Tammewar G, Ayakta N, Baker SL, Bejanin A, Boxer AL, et al. Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer���s disease. Neuroimage Clin. 2018;17:452���64. [PMID: 29159058]
  67. Ossenkoppele R, Schonhaut DR, Sch��ll M, Lockhart SN, Ayakta N, Baker SL, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer���s disease. Brain. 2016;139(Pt 5):1551���67. [PMID: 26962052]
  68. Dronse J, Fliessbach K, Bischof GN, von Reutern B, Faber J, Hammes J, et al. In vivo patterns of tau pathology, amyloid-�� burden, and neuronal dysfunction in clinical variants of Alzheimer���s disease. J Alzheimers Dis. 2017;55(2):465���71. [PMID: 27802224]
  69. Hammond TC, Xing X, Wang C, Ma D, Nho K, Crane PK, et al. ��-amyloid and tau drive early Alzheimer���s disease decline while glucose hypometabolism drives late decline. Commun Biol. 2020;3(1):352. [PMID: 32632135]
  70. Levin F, Ferreira D, Lange C, Dyrba M, Westman E, Buchert R, et al. Data-driven FDG-PET subtypes of Alzheimer���s disease-related neurodegeneration. Alzheimers Res Ther. 2021;13(1):49. [PMID: 33608059]
  71. Chang CW, Evans MD, Yu X, Yu GQ, Mucke L. Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation/inhibition ratios, and counteracts network hypersynchrony. Cell Rep. 2021;37(3):109855. [PMID: 34686344]
  72. Ranasinghe KG, Verma P, Cai C, Xie X, Kudo K, Gao X et al (2022) Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer���s disease. Elife 11. https://doi.org/10.7554/eLife.77850
  73. Fu H, Possenti A, Freer R, Nakano Y, Hernandez Villegas NC, Tang M, et al. A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology. Nat Neurosci. 2019;22(1):47���56. [PMID: 30559469]
  74. 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(1):139. [PMID: 36153607]
  75. 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. [PMID: 27255818]
  76. Najm FJ, Madhavan M, Zaremba A, Shick E, Karl RT, Factor DC, et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature. 2015;522(7555):216���20. [PMID: 25896324]
  77. Cully M. Neurodegenerative diseases: repurposing for remyelination. Nat Rev Drug Discov. 2015;14(6):383. [PMID: 26027533]
  78. Mei F, Lehmann-Horn K, Shen YA, Rankin KA, Stebbins KJ, Lorrain DS et al (2016) Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery. Elife 5. https://doi.org/10.7554/eLife.18246
  79. Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, et al. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017;390(10111):2481���9. [PMID: 29029896]
  80. Scheff SW, Neltner JH, Nelson PT. Is synaptic loss a unique hallmark of Alzheimer���s disease? Biochem Pharmacol. 2014;88(4):517���28. [PMID: 24412275]
  81. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer���s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30(4):572���80. [PMID: 1789684]
  82. Pham E, Crews L, Ubhi K, Hansen L, Adame A, Cartier A, et al. Progressive accumulation of amyloid-beta oligomers in Alzheimer���s disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. Febs j. 2010;277(14):3051���67. [PMID: 20573181]
  83. Vanhaute H, Ceccarini J, Michiels L, Koole M, Sunaert S, Lemmens R, et al. In vivo synaptic density loss is related to tau deposition in amnestic mild cognitive impairment. Neurology. 2020;95(5):e545���53. [PMID: 32493717]
  84. Vanderlinden G, Ceccarini J, Vande Casteele T, Michiels L, Lemmens R, Triau E, et al. Spatial decrease of synaptic density in amnestic mild cognitive impairment follows the tau build-up pattern. Mol Psychiatry. 2022;27(10):4244���51. [PMID: 35794185]
  85. Vogel JW, Corriveau-Lecavalier N, Franzmeier N, Pereira JB, Brown JA, Maass A, et al. Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight. Nat Rev Neurosci. 2023;24(10):620���39. [PMID: 37620599]

Grants

  1. U01 AG024904/NIA NIH HHS

MeSH Term

Humans
Female
Male
tau Proteins
Aged
Alzheimer Disease
Positron-Emission Tomography
Cognitive Dysfunction
Connectome
Magnetic Resonance Imaging
Aged, 80 and over
Cross-Sectional Studies
Brain

Chemicals

tau Proteins
Journal Article
Article has an altmetric score of 11

Word Cloud

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