Skip to main content
SpringerLink
Log in

What Is Neurodegeneration?

  • Chapter
  • First Online:
Molecular Imaging of Neurodegenerative Disorders

  • 429 Accesses

Abstract

Neurodegeneration is a progressive and irreversible process of structural and/or functional loss in neuronal cells, which affects vulnerable cell subsets in certain anatomic brain regions leading to various neurodegenerative diseases. Although the exact etiology of neurodegenerative diseases largely remains unknown, aging is the primary risk factor and some of the main mechanisms underlying neurodegenerative diseases include protein misfolding, protein aggregation, autophagy, lysosomal dysfunction, oxidative injury, mitochondrial dysfunction, and neuroinflammation. Structural MRI, diffusion MRI, arterial spin labeling, MR spectroscopy, FDG, SV2A, beta-amyloid, and tau PET are among common imaging modalities used for neurodegeneration evaluation. Moreover, dopaminergic and cholinergic imaging techniques are used to investigate neurotransmitter systems in neurodegenerative diseases. Emerging imaging techniques of neurodegeneration comprise ultra-field MRI, functional MRI, quantitative susceptibility imaging, and TSPO PET.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Przedborski S, Vila M, Jackson-Lewis V. Neurodegeneration: what is it and where are we? J Clin Invest. 2003;111:3–10. https://doi.org/10.1172/JCI17522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Relja M. Pathophysiology and classification of neurodegenerative diseases. EJIFCC. 2004;15:97–9.

    PubMed  PubMed Central  Google Scholar 

  3. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844–66. https://doi.org/10.1016/j.neuron.2013.10.008.

    Article  CAS  PubMed  Google Scholar 

  4. Bell AH, Miller SL, Castillo-Melendez M, et al. The neurovascular unit: effects of brain insults during the perinatal period. Front Neurosci. 2019;13:1452. https://doi.org/10.3389/fnins.2019.01452.

    Article  PubMed  Google Scholar 

  5. Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96:17–42. https://doi.org/10.1016/j.neuron.2017.07.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Schaeffer S, Iadecola C. Revisiting the neurovascular unit. Nat Neurosci. 2021;24:1198–209. https://doi.org/10.1038/s41593-021-00904-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fan J, Dawson TM, Dawson VL. Cell death mechanisms of neurodegeneration. Adv Neurobiol. 2017;15:403–25. https://doi.org/10.1007/978-3-319-57193-5_16.

    Article  PubMed  Google Scholar 

  8. Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2017;9:a028035. https://doi.org/10.1101/cshperspect.a028035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jellinger KA. Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med. 2010;14:457–87. https://doi.org/10.1111/j.1582-4934.2010.01010.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hartl FU, Hayer-Hartl M. Converging concepts of protein folding in vitro and in vivo. Nat Struct Mol Biol. 2009;16:574–81. https://doi.org/10.1038/nsmb.1591.

    Article  CAS  PubMed  Google Scholar 

  11. Tan SH, Karri V, Tay NWR, et al. Emerging pathways to neurodegeneration: dissecting the critical molecular mechanisms in Alzheimer’s disease, Parkinson’s disease. Biomed Pharmacother. 2019;111:765–77. https://doi.org/10.1016/j.biopha.2018.12.101.

    Article  CAS  PubMed  Google Scholar 

  12. Gan L, Cookson MR, Petrucelli L, et al. Converging pathways in neurodegeneration, from genetics to mechanisms. Nat Neurosci. 2018;21:1300–9. https://doi.org/10.1038/s41593-018-0237-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Menzies FM, Fleming A, Caricasole A, et al. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron. 2017;93:1015–34. https://doi.org/10.1016/j.neuron.2017.01.022.

    Article  CAS  PubMed  Google Scholar 

  14. Ochaba J, Lukacsovich T, Csikos G, et al. Potential function for the Huntingtin protein as a scaffold for selective autophagy. Proc Natl Acad Sci U S A. 2014;111:16889–94. https://doi.org/10.1073/pnas.1420103111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97:1634–58. https://doi.org/10.1111/j.1471-4159.2006.03907.x.

    Article  CAS  PubMed  Google Scholar 

  16. Yang JL, Weissman L, Bohr VA, et al. Mitochondrial DNA damage and repair in neurodegenerative disorders. DNA Repair (Amst). 2008;7:1110–20. https://doi.org/10.1016/j.dnarep.2008.03.012.

    Article  CAS  PubMed  Google Scholar 

  17. Lucin KM, Wyss-Coray T. Immune activation in brain aging and neurodegeneration: too much or too little? Neuron. 2009;64:110–22. https://doi.org/10.1016/j.neuron.2009.08.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hickman S, Izzy S, Sen P, et al. Microglia in neurodegeneration. Nat Neurosci. 2018;21:1359–69. https://doi.org/10.1038/s41593-018-0242-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shimizu S, Hirose D, Hatanaka H, et al. Role of neuroimaging as a biomarker for neurodegenerative diseases. Front Neurol. 2018;9:265. https://doi.org/10.3389/fneur.2018.00265.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Schneider JA, Arvanitakis Z, Bang W, et al. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69:2197–204. https://doi.org/10.1212/01.wnl.0000271090.28148.24.

    Article  PubMed  Google Scholar 

  21. Patel KP, Wymer DT, Bhatia VK, et al. Multimodality imaging of dementia: clinical importance and role of integrated anatomic and molecular imaging. Radiographics. 2020;40:200–22. https://doi.org/10.1148/rg.2020190070.

    Article  PubMed  Google Scholar 

  22. Koikkalainen J, Rhodius-Meester H, Tolonen A, et al. Differential diagnosis of neurodegenerative diseases using structural MRI data. Neuroimage Clin. 2016;11:435–49. https://doi.org/10.1016/j.nicl.2016.02.019.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Karas G, Scheltens P, Rombouts S, et al. Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study. Neuroradiology. 2007;49:967–76. https://doi.org/10.1007/s00234-007-0269-2.

    Article  PubMed  Google Scholar 

  24. Morris JC, Csernansky J, Price JL. MRI measures of entorhinal cortex versus hippocampus in preclinical AD. Neurology. 2002;59:1474; author reply 1474–5. https://doi.org/10.1212/wnl.59.9.1474.

    Article  PubMed  Google Scholar 

  25. Jack CR Jr, Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:257–62. https://doi.org/10.1016/j.jalz.2011.03.004.

    Article  PubMed  PubMed Central  Google Scholar 

  26. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89:88–100. https://doi.org/10.1212/WNL.0000000000004058.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77. https://doi.org/10.1093/brain/awr179.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6. https://doi.org/10.1212/01.wnl.0000324625.00404.15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hoglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32:853–64. https://doi.org/10.1002/mds.26987.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci. 2008;34:51–61. https://doi.org/10.1007/s12031-007-0029-0.

    Article  CAS  PubMed  Google Scholar 

  31. Kamagata K, Andica C, Kato A, et al. Diffusion magnetic resonance imaging-based biomarkers for neurodegenerative diseases. Int J Mol Sci. 2021;22:5216. https://doi.org/10.3390/ijms22105216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Brun A, Englund E. A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study. Ann Neurol. 1986;19:253–62. https://doi.org/10.1002/ana.410190306.

    Article  CAS  PubMed  Google Scholar 

  33. Kantarci K, Murray ME, Schwarz CG, et al. White-matter integrity on DTI and the pathologic staging of Alzheimer’s disease. Neurobiol Aging. 2017;56:172–9. https://doi.org/10.1016/j.neurobiolaging.2017.04.024.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Acosta-Cabronero J, Nestor PJ. Diffusion tensor imaging in Alzheimer’s disease: insights into the limbic-diencephalic network and methodological considerations. Front Aging Neurosci. 2014;6:266. https://doi.org/10.3389/fnagi.2014.00266.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Jacobs HIL, Hedden T, Schultz AP, et al. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci. 2018;21:424–31. https://doi.org/10.1038/s41593-018-0070-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kantarci K, Schwarz CG, Reid RI, et al. White matter integrity determined with diffusion tensor imaging in older adults without dementia: influence of amyloid load and neurodegeneration. JAMA Neurol. 2014;71:1547–54. https://doi.org/10.1001/jamaneurol.2014.1482.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Goveas J, O’Dwyer L, Mascalchi M, et al. Diffusion-MRI in neurodegenerative disorders. Magn Reson Imaging. 2015;33:853–76. https://doi.org/10.1016/j.mri.2015.04.006.

    Article  PubMed  Google Scholar 

  38. Young PNE, Estarellas M, Coomans E, et al. Imaging biomarkers in neurodegeneration: current and future practices. Alzheimers Res Ther. 2020;12:49. https://doi.org/10.1186/s13195-020-00612-7.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nedelska Z, Senjem ML, Przybelski SA, et al. Regional cortical perfusion on arterial spin labeling MRI in dementia with Lewy bodies: associations with clinical severity, glucose metabolism and tau PET. Neuroimage Clin. 2018;19:939–47. https://doi.org/10.1016/j.nicl.2018.06.020.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Wolk DA, Detre JA. Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. Curr Opin Neurol. 2012;25:421–8. https://doi.org/10.1097/WCO.0b013e328354ff0a.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Oz G, Alger JR, Barker PB, et al. Clinical proton MR spectroscopy in central nervous system disorders. Radiology. 2014;270:658–79. https://doi.org/10.1148/radiol.13130531.

    Article  PubMed  Google Scholar 

  42. Kantarci K, Jack CR Jr, Xu YC, et al. Regional metabolic patterns in mild cognitive impairment and Alzheimer’s disease: a 1H MRS study. Neurology. 2000;55:210–7.

    Article  CAS  PubMed  Google Scholar 

  43. Sturrock A, Laule C, Decolongon J, et al. Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease. Neurology. 2010;75:1702–10. https://doi.org/10.1212/WNL.0b013e3181fc27e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kantarci K, Knopman DS, Dickson DW, et al. Alzheimer disease: postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements. Radiology. 2008;248:210–20. https://doi.org/10.1148/radiol.2481071590.

    Article  PubMed  Google Scholar 

  45. Oz G, Hutter D, Tkac I, et al. Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status. Mov Disord. 2010;25:1253–61. https://doi.org/10.1002/mds.23067.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ross BD, Bluml S, Cowan R, et al. In vivo MR spectroscopy of human dementia. Neuroimaging Clin N Am. 1998;8:809–22.

    CAS  PubMed  Google Scholar 

  47. Godbolt AK, Waldman AD, MacManus DG, et al. MRS shows abnormalities before symptoms in familial Alzheimer disease. Neurology. 2006;66:718–22. https://doi.org/10.1212/01.wnl.0000201237.05869.df.

    Article  CAS  PubMed  Google Scholar 

  48. Kantarci K, Boeve BF, Wszolek ZK, et al. MRS in presymptomatic MAPT mutation carriers: a potential biomarker for tau-mediated pathology. Neurology. 2010;75:771–8. https://doi.org/10.1212/WNL.0b013e3181f073c7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Miller BL, Moats RA, Shonk T, et al. Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology. 1993;187:433–7. https://doi.org/10.1148/radiology.187.2.8475286.

    Article  CAS  PubMed  Google Scholar 

  50. Oz G, Iltis I, Hutter D, et al. Distinct neurochemical profiles of spinocerebellar ataxias 1, 2, 6, and cerebellar multiple system atrophy. Cerebellum. 2011;10:208–17. https://doi.org/10.1007/s12311-010-0213-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rupsingh R, Borrie M, Smith M, et al. Reduced hippocampal glutamate in Alzheimer disease. Neurobiol Aging. 2011;32:802–10. https://doi.org/10.1016/j.neurobiolaging.2009.05.002.

    Article  CAS  PubMed  Google Scholar 

  52. Krishnan KR, Charles HC, Doraiswamy PM, et al. Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer’s disease. Am J Psychiatry. 2003;160:2003–11. https://doi.org/10.1176/appi.ajp.160.11.2003.

    Article  PubMed  Google Scholar 

  53. Bartha R, Smith M, Rupsingh R, et al. High field (1)H MRS of the hippocampus after donepezil treatment in Alzheimer disease. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32:786–93. https://doi.org/10.1016/j.pnpbp.2007.12.011.

    Article  CAS  Google Scholar 

  54. Lim SM, Katsifis A, Villemagne VL, et al. The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J Nucl Med. 2009;50:1638–45. https://doi.org/10.2967/jnumed.109.065870.

    Article  CAS  PubMed  Google Scholar 

  55. Graff-Radford J, Murray ME, Lowe VJ, et al. Dementia with Lewy bodies: basis of cingulate island sign. Neurology. 2014;83:801–9. https://doi.org/10.1212/WNL.0000000000000734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Shankar GM, Walsh DM. Alzheimer’s disease: synaptic dysfunction and Abeta. Mol Neurodegener. 2009;4:48. https://doi.org/10.1186/1750-1326-4-48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Scheff SW, Price DA, Schmitt FA, et al. Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–84. https://doi.org/10.1016/j.neurobiolaging.2005.09.012.

    Article  CAS  PubMed  Google Scholar 

  58. Hou Z, Lei H, Hong S, et al. Functional changes in the frontal cortex in Parkinson’s disease using a rat model. J Clin Neurosci. 2010;17:628–33. https://doi.org/10.1016/j.jocn.2009.07.101.

    Article  CAS  PubMed  Google Scholar 

  59. Cai Z, Li S, Matuskey D, et al. PET imaging of synaptic density: a new tool for investigation of neuropsychiatric diseases. Neurosci Lett. 2019;691:44–50. https://doi.org/10.1016/j.neulet.2018.07.038.

    Article  CAS  PubMed  Google Scholar 

  60. Bajjalieh SM, Frantz GD, Weimann JM, et al. Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J Neurosci. 1994;14:5223–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Finnema SJ, Nabulsi NB, Eid T, et al. Imaging synaptic density in the living human brain. Sci Transl Med. 2016;8:348–96. https://doi.org/10.1126/scitranslmed.aaf6667.

    Article  CAS  Google Scholar 

  62. Jack CR Jr, Lowe VJ, Senjem ML, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain. 2008;131:665–80. https://doi.org/10.1093/brain/awm336.

    Article  PubMed  Google Scholar 

  63. Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55:306–19. Comparative Study Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. https://doi.org/10.1002/ana.20009.

    Article  CAS  PubMed  Google Scholar 

  64. Chetelat G, Arbizu J, Barthel H, et al. Amyloid-PET and (18)F-FDG-PET in the diagnostic investigation of Alzheimer’s disease and other dementias. Lancet Neurol. 2020;19:951–62. https://doi.org/10.1016/S1474-4422(20)30314-8.

    Article  CAS  PubMed  Google Scholar 

  65. Jansen WJ, Ossenkoppele R, Knol DL, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38. https://doi.org/10.1001/jama.2015.4668.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Mallik A, Drzezga A, Minoshima S. Clinical amyloid imaging. Semin Nucl Med. 2017;47:31–43. https://doi.org/10.1053/j.semnuclmed.2016.09.005.

    Article  PubMed  Google Scholar 

  67. Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. J Nucl Med. 2013;54:476–90. https://doi.org/10.2967/jnumed.113.120618.

    Article  CAS  PubMed  Google Scholar 

  68. Buee L, Bussiere T, Buee-Scherrer V, et al. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev. 2000;33:95–130. https://doi.org/10.1016/s0165-0173(00)00019-9.

    Article  CAS  PubMed  Google Scholar 

  69. Chien DT, Bahri S, Szardenings AK, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34:457–68. https://doi.org/10.3233/JAD-122059.

    Article  CAS  PubMed  Google Scholar 

  70. Groot C, Villeneuve S, Smith R, et al. Tau PET imaging in neurodegenerative disorders. J Nucl Med. 2022;63:20S–6S. https://doi.org/10.2967/jnumed.121.263196.

    Article  CAS  PubMed  Google Scholar 

  71. Nelson PT, Alafuzoff I, Bigio EH, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol. 2012;71:362–81. https://doi.org/10.1097/NEN.0b013e31825018f7.

    Article  PubMed  Google Scholar 

  72. Graebner AK, Tarsy D, Shih LC, et al. Clinical impact of 123I-Ioflupane SPECT (DaTscan) in a movement disorder center. Neurodegener Dis. 2017;17:38–43. https://doi.org/10.1159/000447561.

    Article  CAS  PubMed  Google Scholar 

  73. Palermo G, Ceravolo R. Molecular imaging of the dopamine transporter. Cells. 2019;8:872. https://doi.org/10.3390/cells8080872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kerstens VS, Fazio P, Sundgren M, et al. Reliability of dopamine transporter PET measurements with [(18)F]FE-PE2I in patients with Parkinson’s disease. EJNMMI Res. 2020;10:95. https://doi.org/10.1186/s13550-020-00676-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30:1591–601. https://doi.org/10.1002/mds.26424.

    Article  PubMed  Google Scholar 

  76. Sakakibara S, Hashimoto R, Katayama T, et al. Longitudinal change of DAT SPECT in Parkinson’s disease and multiple system atrophy. J Parkinsons Dis. 2020;10:123–30. https://doi.org/10.3233/JPD-191710.

    Article  CAS  PubMed  Google Scholar 

  77. Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson’s disease. Brain. 2011;134:3290–8. https://doi.org/10.1093/brain/awr233.

    Article  PubMed  Google Scholar 

  78. Ibrahim N, Kusmirek J, Struck AF, et al. The sensitivity and specificity of F-DOPA PET in a movement disorder clinic. Am J Nucl Med Mol Imaging. 2016;6:102–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Morrish PK, Sawle GV, Brooks DJ. Clinical and [18F] dopa PET findings in early Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1995;59:597–600. https://doi.org/10.1136/jnnp.59.6.597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Pavese N, Brooks DJ. Imaging neurodegeneration in Parkinson’s disease. Biochim Biophys Acta. 2009;1792:722–9. https://doi.org/10.1016/j.bbadis.2008.10.003.

    Article  CAS  PubMed  Google Scholar 

  81. Berger-Sweeney J. The cholinergic basal forebrain system during development and its influence on cognitive processes: important questions and potential answers. Neurosci Biobehav Rev. 2003;27:401–11. https://doi.org/10.1016/s0149-7634(03)00070-8.

    Article  CAS  PubMed  Google Scholar 

  82. Roy R, Niccolini F, Pagano G, et al. Cholinergic imaging in dementia spectrum disorders. Eur J Nucl Med Mol Imaging. 2016;43:1376–86. https://doi.org/10.1007/s00259-016-3349-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bohnen NI, Kaufer DI, Hendrickson R, et al. Cognitive correlates of alterations in acetylcholinesterase in Alzheimer’s disease. Neurosci Lett. 2005;380:127–32. https://doi.org/10.1016/j.neulet.2005.01.031.

    Article  CAS  PubMed  Google Scholar 

  84. Kuhl DE, Minoshima S, Fessler JA, et al. In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol. 1996;40:399–410. https://doi.org/10.1002/ana.410400309.

    Article  CAS  PubMed  Google Scholar 

  85. Kaasinen V, Nagren K, Jarvenpaa T, et al. Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer’s disease. J Clin Psychopharmacol. 2002;22:615–20. https://doi.org/10.1097/00004714-200212000-00012.

    Article  CAS  PubMed  Google Scholar 

  86. Klein JC, Eggers C, Kalbe E, et al. Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo. Neurology. 2010;74:885–92. https://doi.org/10.1212/WNL.0b013e3181d55f61.

    Article  CAS  PubMed  Google Scholar 

  87. Versluis MJ, van der Grond J, van Buchem MA, et al. High-field imaging of neurodegenerative diseases. Neuroimaging Clin N Am. 2012;22:159–71, ix. https://doi.org/10.1016/j.nic.2012.02.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang N, Song X, Bartha R, et al. Advances in high-field magnetic resonance spectroscopy in Alzheimer’s disease. Curr Alzheimer Res. 2014;11:367–88. https://doi.org/10.2174/1567205011666140302200312.

  89. Barker PB, Hearshen DO, Boska MD. Single-voxel proton MRS of the human brain at 1.5T and 3.0T. Magn Reson Med. 2001;45:765–9. https://doi.org/10.1002/mrm.1104.

    Article  CAS  PubMed  Google Scholar 

  90. Tkac I, Andersen P, Adriany G, et al. In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn Reson Med. 2001;46:451–6. https://doi.org/10.1002/mrm.1213.

    Article  CAS  PubMed  Google Scholar 

  91. Hohenfeld C, Werner CJ, Reetz K. Resting-state connectivity in neurodegenerative disorders: is there potential for an imaging biomarker? Neuroimage Clin. 2018;18:849–70. https://doi.org/10.1016/j.nicl.2018.03.013.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Smitha KA, Akhil Raja K, Arun KM, et al. Resting state fMRI: a review on methods in resting state connectivity analysis and resting state networks. Neuroradiol J. 2017;30:305–17. https://doi.org/10.1177/1971400917697342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Filippi M, Spinelli EG, Cividini C, et al. Resting state dynamic functional connectivity in neurodegenerative conditions: a review of magnetic resonance imaging findings. Front Neurosci. 2019;13:657. https://doi.org/10.3389/fnins.2019.00657.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Seeley WW, Crawford RK, Zhou J, et al. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62:42–52. https://doi.org/10.1016/j.neuron.2009.03.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mills E, Dong XP, Wang F, et al. Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders. Future Med Chem. 2010;2:51–64. https://doi.org/10.4155/fmc.09.140.

    Article  CAS  PubMed  Google Scholar 

  96. Morris G, Berk M, Carvalho AF, et al. Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases. Behav Brain Res. 2018;341:154–75. https://doi.org/10.1016/j.bbr.2017.12.036.

    Article  CAS  PubMed  Google Scholar 

  97. Ndayisaba A, Kaindlstorfer C, Wenning GK. Iron in neurodegeneration - cause or consequence? Front Neurosci. 2019;13:180. https://doi.org/10.3389/fnins.2019.00180.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Langkammer C, Schweser F, Krebs N, et al. Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study. Neuroimage. 2012;62:1593–9. https://doi.org/10.1016/j.neuroimage.2012.05.049.

    Article  PubMed  Google Scholar 

  99. Haacke EM, Liu S, Buch S, et al. Quantitative susceptibility mapping: current status and future directions. Magn Reson Imaging. 2015;33:1–25. https://doi.org/10.1016/j.mri.2014.09.004.

    Article  PubMed  Google Scholar 

  100. Ravanfar P, Loi SM, Syeda WT, et al. Systematic review: quantitative susceptibility mapping (QSM) of brain iron profile in neurodegenerative diseases. Front Neurosci. 2021;15:618435. https://doi.org/10.3389/fnins.2021.618435.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Chen Q, Boeve BF, Forghanian-Arani A, et al. MRI quantitative susceptibility mapping of the substantia nigra as an early biomarker for Lewy body disease. J Neuroimaging. 2021;31:1020–7. https://doi.org/10.1111/jon.12878.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Werry EL, Bright FM, Piguet O, et al. Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders. Int J Mol Sci. 2019;20:3161. https://doi.org/10.3390/ijms20133161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Tournier BB, Tsartsalis S, Ceyzeriat K, et al. In vivo TSPO signal and neuroinflammation in Alzheimer’s disease. Cells. 2020;9:1941. https://doi.org/10.3390/cells9091941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Hamelin L, Lagarde J, Dorothee G, et al. Early and protective microglial activation in Alzheimer’s disease: a prospective study using 18F-DPA-714 PET imaging. Brain. 2016;139:1252–64. https://doi.org/10.1093/brain/aww017.

    Article  PubMed  Google Scholar 

  105. Lavisse S, Goutal S, Wimberley C, et al. Increased microglial activation in patients with Parkinson disease using [(18)F]-DPA714 TSPO PET imaging. Parkinsonism Relat Disord. 2021;82:29–36. https://doi.org/10.1016/j.parkreldis.2020.11.011.

    Article  CAS  PubMed  Google Scholar 

  106. Sucksdorff M, Matilainen M, Tuisku J, et al. Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis. Brain. 2020;143:3318–30. https://doi.org/10.1093/brain/awaa275.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Kantarci K. 2021 marks a new era for Alzheimer’s therapeutics. Lancet Neurol. 2022;21:3–4. https://doi.org/10.1016/S1474-4422(21)00412-9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    Burcu Zeydan & Kejal Kantarci

  2. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Burcu Zeydan

Authors
  1. Burcu Zeydan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kejal Kantarci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Burcu Zeydan .

Editor information

Editors and Affiliations

  1. Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, USA

    Donna J. Cross

  2. Department of Nuclear Medicine, Hospital das Forças Armadas (HFA), Brasilia, Distrito Federal, Brazil

    Karina Mosci

  3. Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, USA

    Satoshi Minoshima

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zeydan, B., Kantarci, K. (2023). What Is Neurodegeneration?. In: Cross, D.J., Mosci, K., Minoshima, S. (eds) Molecular Imaging of Neurodegenerative Disorders. Springer, Cham. https://doi.org/10.1007/978-3-031-35098-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-35098-6_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-35097-9

  • Online ISBN: 978-3-031-35098-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation