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Cited by 52Functional Brain Connectivity StudiesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The network degeneration hypothesis: spread of neurodegenerative patterns along neuronal brain networks

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Drzezga, Alexander·2018·Journal of Nuclear Medicine
DOI 10.2967/jnumed.117.206300
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Abstract

The network degeneration hypothesis suggests that neurodegenerative disorders are characterized by the spread of molecular neuropathologic features along specific neuronal brain networks, leading to functional impairment of these networks. Interestingly, the symptomatic phenotype of

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  • Human studies based on functional connectivity and tractography have suggested brain networks could play a role in tauopathy progression, consistent with the prion hypothesis.

    “Human studies based on functional connectivity and tractography have suggested brain networks could play a role in tauopathy progression, consistent with the prion hypothesis (Braak and Braak, 1991; Seeley et al., 2009; Drzezga, 2018; Frontzkowski et al., 2022).”

    From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Drzezga, 2018

    The main text (page not provided) reports human tau-imaging findings that overlap with functional brain networks and discusses possible prionlike spread of tau along those networks. It does not describe tractography-based human studies, so that methodological detail is unsupported by this source. (LLM, conf=0.84)

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Research works printed but not linked: 39

  1. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676-682.
  2. Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA. 2003;100:253-258.
  3. Buckner RL, Krienen FM, Yeo BT. Opportunities and limitations of intrinsic functional connectivity MRI. Nat Neurosci. 2013;16:832-837.
  4. Van Dijk KR, Hedden T, Venkataraman A, Evans KC, Lazar SW, Buckner RL. Intrinsic functional connectivity as a tool for human connectomics: theory, prop- erties, and optimization. J Neurophysiol. 2010;103:297-321.
  5. Yeo BT, Krienen FM, Sepulcre J, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:1125-1165.
  6. Lu H, Zou Q, Gu H, Raichle ME, Stein EA, Yang Y. Rat brains also have a default mode network. Proc Natl Acad Sci USA. 2012;109:3979-3984.
  7. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124: 1-38.
  8. Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62:42-52.
  9. Raj A, Kuceyeski A, Weiner M. A network diffusion model of disease progres- sion in dementia. Neuron. 2012;73:1204-1215.
  10. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol. 1997;42:85-94.
  11. Minoshima S, Foster NL, Sima AA, Frey KA, Albin RL, Kuhl DE. Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol. 2001;50:358-365.
  12. Drzezga A, Lautenschlager N, Siebner H, et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Mol Imaging. 2003;30:1104-1113.
  13. Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in ''probable'' Alzheimer's disease and normal ageing: diagnostic value and neuro- psychological correlates. J Neurol Neurosurg Psychiatry. 1992;55:967-972.
  14. Dickerson BC, Bakkour A, Salat DH, et al. The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex. 2009;19:497-510.
  15. Sorg C, Riedl V, Muhlau M, et al. Selective changes of resting-state networks in individuals at risk for Alzheimer's disease. Proc Natl Acad Sci USA. 2007;104: 18760-18765.
  16. Hedden T, Van Dijk KR, Becker JA, et al. Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J Neurosci. 2009;29: 12686-12694.
  17. Bischof GN, Jessen F, Fliessbach K, et al. Impact of tau and amyloid burden on glucose metabolism in Alzheimer's disease. Ann Clin Transl Neurol. 2016;3:934- 939.
  18. Drzezga A, Becker JA, Van Dijk KR, et al. Neuronal dysfunction and discon- nection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain. 2011;134:1635-1646.
  19. Jack CR Jr, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207-216.
  20. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging- Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:280-292.
  21. Jack CR Jr, Bennett DA, Blennow K, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87:539- 547.
  22. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guide- lines for Alzheimer's disease. Alzheimers Dement. 2011;7:270-279.
  23. Hoenig MC, Bischof GN, Seemiller J, et al. Networks of tau distribution in Alzheimer's disease. Brain. 2018;141:568-581.
  24. Cope TE, Rittman T, Borchert RJ, et al. Tau burden and the functional connec- tome in Alzheimer's disease and progressive supranuclear palsy. Brain. 2018;141: 550-567.
  25. Dronse J, Fliessbach K, Bischof GN, et al. In vivo patterns of tau pathology, amyloid-beta burden, and neuronal dysfunction in clinical variants of Alzheimer's disease. J Alzheimers Dis. 2017;55:465-471.
  26. Ossenkoppele R, Schonhaut DR, Scholl M, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain. 2016;139:1551-1567.
  27. Bonner MF, Ash S, Grossman M. The new classification of primary progressive aphasia into semantic, logopenic, or nonfluent/agrammatic variants. Curr Neurol Neurosci Rep. 2010;10:484-490.
  28. Diehl-Schmid J, Onur OA, Kuhn J, Gruppe T, Drzezga A. Imaging frontotem- poral lobar degeneration. Curr Neurol Neurosci Rep. 2014;14:489.
  29. Tahmasian M, Shao J, Meng C, et al. Based on the network degeneration hypoth- esis: separating individual patients with different neurodegenerative syndromes in a preliminary hybrid PET/MR study. J Nucl Med. 2016;57:410-415.
  30. Warren JD, Rohrer JD, Schott JM, Fox NC, Hardy J, Rossor MN. Molecular nexopathies: a new paradigm of neurodegenerative disease. Trends Neurosci. 2013;36: 561-569.
  31. Ahmed RM, Devenney EM, Irish M, et al. Neuronal network disintegration: common pathways linking neurodegenerative diseases. J Neurol Neurosurg Psy- chiatry. 2016;87:1234-1241.
  32. Swaab DF. Brain aging and Alzheimer's disease, ''wear and tear'' versus ''use it or lose it.'' Neurobiol Aging. 1991;12:317-324.
  33. Cirrito JR, Yamada KA, Finn MB, et al. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron. 2005;48:913-922.
  34. Selkoe DJ. Soluble oligomers of the amyloid beta-protein impair synaptic plas- ticity and behavior. Behav Brain Res. 2008;192:106-113.
  35. 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;107:17757-17762
  36. Braak H, Del Tredici K. Alzheimer's pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol (Berl). 2011;121:589-595.
  37. Iba M, Guo JL, McBride JD, Zhang B, Trojanowski JQ, Lee VM. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy. J Neurosci. 2013;33:1024-1037.
  38. Liu L, Drouet V, Wu JW, et al. Trans-synaptic spread of tau pathology in vivo. PLoS One. 2012;7:e31302.
  39. Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370:322-333.

Cited by

Sorted by citations

Authors
Drzezga, A.
Affiliations
German Center for Neurodegenerative Diseases (DE)
Corresponding author
Drzezga, Alexander
ORCID
Drzezga, Alexander
Venue
Journal of Nuclear Medicine
Publisher
Society of Nuclear Medicine
Published
2018-11
Volume
59
Issue
11
Pages
1645-1648
ISSN
  • 0161-5505 (ISSN-L)
  • 2159-662X
DOI
10.2967/jnumed.117.206300
OpenAlex
W2899506695
Cited by
52
References
7
Citations by year
2026: 5 · 2025: 10 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 1
FWCI
0.50
Type
journal article
Language
en
Open access
Locations
  • Journal of Nuclear Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • DZNE Pub (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
neurodegenerative diseases, functional disability
MeSH terms
Alzheimer Disease, Brain, Humans, Magnetic Resonance Imaging, Models, Neurological, Nerve Degeneration, Nerve Net, tau Proteins, Neurodegenerative Diseases, Positron-Emission Tomography, Functional Neuroimaging, Protein Aggregation, Pathological

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