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Age-related increase of monoamine oxidase B in amyloid-negative cognitively unimpaired elderly subjects

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Abstract

Objective

Monoamine oxidase B (MAO-B) is highly abundant in reactive astrocytes and upregulated in neuroinflammatory processes. However, the age-related change of MAO-B in amyloid-negative cognitively unimpaired elderly subjects has not yet been sufficiently evaluated on positron emission tomography (PET). 18F-THK5351 is a radiotracer with high affinity to MAO-B, which may potentially serve as an imaging biomarker for detecting neuroinflammation. The purpose of this study was to investigate the age-related topographic change of 18F-THK5351 PET in amyloid-negative cognitively unimpaired elderly subjects.

Methods

The age-related change of 18F-THK5351 retention was evaluated on the visual analysis, voxel and region of interest (ROI)-based analyses using Statistical Parametric Mapping and PETSurfer tool of FreeSurfer in 31 amyloid-negative cognitively unimpaired elderly subjects.

Results

On visual inspection, elderly groups showed the spread of 18F-THK5351 accumulation from the medial to inferolateral temporal and basal frontal lobes, and cingulate gyrus. Additionally, voxel- and ROI-based analysis demonstrated the correlation between 18F-THK5351 accumulation and participants’ age, especially in the inferior temporal lobes.

Conclusions

This study demonstrated age-dependent increase of 18F-THK5351 retention in amyloid-negative cognitively unimpaired subjects, which suggests an increase in MAO-B positive reactive astrocytes with aging.

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References

  1. Damier P, Kastner A, Agid Y, Hirsch EC. Does monoamine oxidase type B play a role in dopaminergic nerve cell death in Parkinson’s disease? Neurology. 1996;46:1262–9.

    Article  CAS  Google Scholar 

  2. Riederer P, Konradi C, Schay V, Kienzl E, Birkmayer G, Danielczyk W, Sofic E, Youdim MB. Localization of MAO-A and MAO-B in human brain: a step in understanding the therapeutic action of L-deprenyl. Adv Neurol. 1987;45:111–8.

    CAS  PubMed  Google Scholar 

  3. Saura J, Andrés N, Andrade C, Ojuel J, Eriksson K, Mahy N. Biphasic and region-specific MAO-B response to aging in normal human brain. Neurobiol Aging. 1997;18:497–507.

    Article  CAS  Google Scholar 

  4. Fowler JS, Volkow ND, Wang GJ, Logan J, Pappas N, Shea C, MacGregor R. Age-related increases in brain monoamine oxidase B in living healthy human subjects. Neurobiol Aging. 1997;18:431–5.

    Article  CAS  Google Scholar 

  5. Alper G, Girgin FK, Ozgönül M, Menteş G, Ersöz B. MAO inhibitors and oxidant stress in aging brain tissue. Eur Neuropsychopharmacol. 1999;9:247–52.

    Article  CAS  Google Scholar 

  6. Palmer AL, Ousman SS. Astrocytes and aging. Front Aging Neurosci. 2018;10:337.

    Article  CAS  Google Scholar 

  7. Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, Tago T, Hiraoka K, Watanuki S, Shidahara M, Miyake M, Ishikawa Y, Matsuda R, Inami A, Yoshikawa T, Funaki Y, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y. 18F-THK5351: a Novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer disease. J Nucl Med. 2016;57:208–14.

    Article  CAS  Google Scholar 

  8. Lee H, Seo S, Lee SY, Jeong HJ, Woo SH, Lee KM, Lee YB, Park KH, Heo JH, Yoon CW, Kang JM, Cho J, Okamura N, Furumoto S, Yanai K, Na DL, Ido T, Villemagne VL, Noh Y. [18F]-THK5351 PET imaging in patients with semantic variant primary progressive aphasia. Alzheimer Dis Assoc Disord. 2018;32:62–9.

    Article  Google Scholar 

  9. Ng KP, Pascoal TA, Mathotaarachchi S, Therriault J, Kang MS, Shin M, Guiot MC, Guo Q, Harada R, Comley RA, Massarweh G, Soucy JP, Okamura N, Gauthier S, Rosa-Neto P. Monoamine oxidase B inhibitor, selegiline, reduces (18)F-THK5351 uptake in the human brain. Alzheimers Res Ther. 2017;9:25.

    Article  Google Scholar 

  10. Harada R, Ishiki A, Kai H, Sato N, Furukawa K, Furumoto S, Tago T, Tomita N, Watanuki S, Hiraoka K, Ishikawa Y, Funaki Y, Nakamura T, Yoshikawa T, Iwata R, Tashiro M, Sasano H, Kitamoto T, Yanai K, Arai H, Kudo Y, Okamura N. Correlations of (18)F-THK5351 PET with postmortem burden of tau and astrogliosis in Alzheimer disease. J Nucl Med. 2018;59:671–4.

    Article  CAS  Google Scholar 

  11. Ishibashi K, Kameyama M, Miura Y, Toyohara J, Ishii K. Head-to-head comparison of the two MAO-B radioligands, 18F-THK5351 and 11C-L-deprenyl, to visualize astrogliosis in patients with neurological disorders. Clin Nucl Med. 2021;46:e31–3.

    Article  Google Scholar 

  12. Gulyás B, Pavlova E, Kása P, Gulya K, Bakota L, Várszegi S, Keller E, Horváth MC, Nag S, Hermecz I, Magyar K, Halldin C. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography. Neurochem Int. 2011;58:60–8.

    Article  Google Scholar 

  13. Kang JM, Lee SY, Seo S, Jeong HJ, Woo SH, Lee H, Lee YB, Yeon BK, Shin DH, Park KH, Kang H, Okamura N, Furumoto S, Yanai K, Villemagne VL, Seong JK, Na DL, Ido T, Cho J, Lee KM, Noh Y. Tau positron emission tomography using [(18)F]THK5351 and cerebral glucose hypometabolism in Alzheimer’s disease. Neurobiol Aging. 2017;59:210–9.

    Article  CAS  Google Scholar 

  14. Huang CC, Hsiao IT, Huang CY, Weng YC, Huang KL, Liu CH, Chang TY, Wu HC, Yen TC, Lin KJ. Tau PET With (18)F-THK-5351 Taiwan Patients With Familial Alzheimer’s Disease With the APP p. D678H Mutation. Front Neurol. 2019;10:503.

    Article  Google Scholar 

  15. Jeon S, Kang JM, Seo S, Jeong HJ, Funck T, Lee SY, Park KH, Lee YB, Yeon BK, Ido T, Okamura N, Evans AC, Na DL, Noh Y. Topographical heterogeneity of Alzheimer’s disease based on MR imaging, tau PET, and amyloid PET. Front Aging Neurosci. 2019;11:211.

    Article  CAS  Google Scholar 

  16. Shigemoto Y, Sone D, Ota M, Maikusa N, Ogawa M, Okita K, Takano H, Kato K, Kimura Y, Morimoto E, Suzuki F, Fujii H, Sato N, Matsuda H. Voxel-based correlation of (18)F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults. EJNMMI Res. 2019;9:81.

    Article  Google Scholar 

  17. Jeong HJ, Lee H, Lee SY, Seo S, Park KH, Lee YB, Shin DJ, Kang JM, Yeon BK, Kang SG, Cho J, Seong JK, Okamura N, Villemagne VL, Na DL, Noh Y. [18F]THK5351 PET imaging in patients with mild cognitive impairment. J Clin Neurol. 2020;16:202–14.

    Article  Google Scholar 

  18. Nihashi T, Sakurai K, Kato T, Iwata K, Kimura Y, Ikenuma H, Yamaoka A, Takeda A, Arahata Y, Washimi Y, Suzuki K, Bundo M, Sakurai T, Okamura N, Yanai K, Ito K, Nakamura A. Patterns of distribution of 18F-THK5351 positron emission tomography in Alzheimer’s disease continuum. J Alzheimers Dis. 2022;85:223–34.

    Article  CAS  Google Scholar 

  19. Iwatsubo T, Iwata A, Suzuki K, Ihara R, Arai H, Ishii K, Senda M, Ito K, Ikeuchi T, Kuwano R, Matsuda H, Sun CK, Beckett LA, Petersen RC, Weiner MW, Aisen PS, Donohue MC. Japanese and north American Alzheimer’s disease neuroimaging initiative studies: harmonization for international trials. Alzheimers Dement. 2018;14:1077–87.

    Article  Google Scholar 

  20. Nakamura A, Cuesta P, Kato T, Arahata Y, Iwata K, Yamagishi M, Kuratsubo I, Kato K, Bundo M, Diers K, Fernández A, Maestú F, Ito K. Early functional network alterations in asymptomatic elders at risk for Alzheimer’s disease. Sci Rep. 2017;7:6517.

    Article  Google Scholar 

  21. Okada Y, Kato T, Iwata K, Kimura Y, Nakamura A, Hattori H, Toyama H, Ishii K, Ishii K, Senda M, Ito K, Iwatsubo T. Evaluation of PiB visual interpretation with CSF Aβ and longitudinal SUVR in J-ADNI study. Ann Nucl Med. 2020;34:108–18.

    Article  CAS  Google Scholar 

  22. Lockhart SN, Baker SL, Okamura N, Furukawa K, Ishiki A, Furumoto S, Tashiro M, Yanai K, Arai H, Kudo Y, Harada R, Tomita N, Hiraoka K, Watanuki S, Jagust WJ. Dynamic PET measures of tau accumulation in cognitively normal older adults and Alzheimer’s disease patients measured using [18F] THK-5351. PLoS One. 2016;11:e0158460.

    Article  Google Scholar 

  23. Greve DN, Svarer C, Fisher PM, Feng L, Hansen AE, Baare W, Rosen B, Fischl B, Knudsen GM. Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data. Neuroimage. 2014;92:225–36.

    Article  Google Scholar 

  24. Tong J, Meyer JH, Furukawa Y, Boileau I, Chang LJ, Wilson AA, Houle S, Kish SJ. Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies. J Cereb Blood Flow Metab. 2013;33:863–71.

    Article  CAS  Google Scholar 

  25. Jang YK, Lyoo CH, Park S, Oh SJ, Cho H, Oh M, Ryu YH, Choi JY, Rabinovici GD, Kim HJ, Moon SH, Jang H, Lee JS, Jagust WJ, Na DL, Kim JS, Seo SW. Head to head comparison of [(18)F] AV-1451 and [(18)F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia. Eur J Nucl Med Mol Imaging. 2018;45:432–42.

    Article  CAS  Google Scholar 

  26. Soreq L, Rose J, Soreq E, Hardy J, Trabzuni D, Cookson MR, Smith C, Ryten M, Patani R, Ule J. Major shifts in glial regional identity are a transcriptional hallmark of human brain aging. Cell Rep. 2017;18:557–70.

    Article  CAS  Google Scholar 

  27. Carter SF, Herholz K, Rosa-Neto P, Pellerin L, Nordberg A, Zimmer ER. Astrocyte biomarkers in Alzheimer’s disease. Trends Mol Med. 2019;25:77–95.

    Article  CAS  Google Scholar 

  28. Villemagne VL, Harada R, Dore V, Furumoto S, Mulligan R, Kudo Y, Burnham S, Krishnadas N, Bozinovski S, Huang K, Lopresti BJ, Yanai K, Rowe CC, Okamura N. First-in-human evaluation of (18)F-SMBT-1, a novel (18)F-labeled MAO-B PET tracer for imaging reactive astrogliosis. J Nucl Med. 2022. https://doi.org/10.2967/jnumed.121.263254.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Chinta SJ, Woods G, Rane A, Demaria M, Campisi J, Andersen JK. Cellular senescence and the aging brain. Exp Gerontol. 2015;68:3–7.

    Article  CAS  Google Scholar 

  30. Nekrasov PV, Vorobyov VV. Dopaminergic mediation in the brain aging and neurodegenerative diseases: a role of senescent cells. Neural Regen Res. 2018;13:649–50.

    Article  CAS  Google Scholar 

  31. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.

    Article  CAS  Google Scholar 

  32. Schöll M, Lockhart SN, Schonhaut DR, O’Neil JP, Janabi M, Ossenkoppele R, Baker SL, Vogel JW, Faria J, Schwimmer HD, Rabinovici GD, Jagust WJ. PET Imaging of tau deposition in the aging human brain. Neuron. 2016;89:971–82.

    Article  Google Scholar 

  33. Pontecorvo MJ, Devous MD Sr, Navitsky M, Lu M, Salloway S, Schaerf FW, Jennings D, Arora AK, McGeehan A, Lim NC, Xiong H, Joshi AD, Siderowf A, Mintun MA. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain. 2017;140:748–63.

    PubMed  PubMed Central  Google Scholar 

  34. Lowe VJ, Bruinsma TJ, Min HK, Lundt ES, Fang P, Senjem ML, Boeve BF, Josephs KA, Pandey MK, Murray ME, Kantarci K, Jones DT, Schwarz CG, Knopman DS, Petersen RC, Jack CR Jr. Elevated medial temporal lobe and pervasive brain tau-PET signal in normal participants. Alzheimers Dement (Amst). 2018;10:210–6.

    Article  Google Scholar 

  35. Lowe VJ, Wiste HJ, Senjem ML, Weigand SD, Therneau TM, Boeve BF, Josephs KA, Fang P, Pandey MK, Murray ME, Kantarci K, Jones DT, Vemuri P, Graff-Radford J, Schwarz CG, Machulda MM, Mielke MM, Roberts RO, Knopman DS, Petersen RC, Jack CR Jr. Widespread brain tau and its association with ageing, braak stage and Alzheimer’s dementia. Brain. 2018;141:271–87.

    Article  Google Scholar 

  36. Son HJ, Oh JS, Roh JH, Seo SW, Oh M, Lee SJ, Oh SJ, Kim JS. Differences in gray and white matter (18)F-THK5351 uptake between behavioral-variant frontotemporal dementia and other dementias. Eur J Nucl Med Mol Imaging. 2019;46:357–66.

    Article  CAS  Google Scholar 

  37. Oyama S, Hosoi A, Ibaraki M, McGinnity CJ, Matsubara K, Watanuki S, Watabe H, Tashiro M, Shidahara M. Error propagation analysis of seven partial volume correction algorithms for [(18)F]THK-5351 brain PET imaging. EJNMMI Phys. 2020;7:57.

    Article  Google Scholar 

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Acknowledgements

We thank Mr. John Gelblum for his English proofreading.

Funding

This research was supported by AMED (20ae0101077h0003) and an in-house grants in National Center for Geriatrics and Gerontology (23–36, 26–30, 27–4, 29–24, 30–3). The authors are grateful to all the staff members of the National Center for Geriatrics and Gerontology for their contribution to the MULNIAD and ADSAT studies.

Author information

Authors and Affiliations

  1. Department of Radiology, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan

    Keita Sakurai, Takashi Nihashi, Kengo Ito & Takashi Kato

  2. Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan

    Yasuyuki Kimura, Kaori Iwata, Hiroshi Ikenuma, Kengo Ito, Takashi Kato & Akinori Nakamura

  3. Department of Neurology, National Center for Geriatrics and Gerontology, Obu, Japan

    Yutaka Arahata

  4. Division of Pharmacology, Faculty of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Nobuyuki Okamura

  5. Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan

    Kazuhiko Yanai

  6. Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan

    Akio Akagi

  7. Department of Biomarker Research, National Center for Geriatrics and Gerontology, Obu, Japan

    Akinori Nakamura

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  1. Keita Sakurai
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  2. Takashi Nihashi
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  3. Yasuyuki Kimura
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  8. Kazuhiko Yanai
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  10. Kengo Ito
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  11. Takashi Kato
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  12. Akinori Nakamura
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Corresponding author

Correspondence to Takashi Kato.

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Conflict of interest

Prof. Okamura received a research grant from GE Healthcare and own stock in Clino Ltd. Other authors have no conflict of interest to report.

Ethical approval

We declare that all human and animal studies have been approved by the Ethics Committee of NCGG, and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Participants were all fully informed of the study procedures and have signed the informed consent.

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Sakurai, K., Nihashi, T., Kimura, Y. et al. Age-related increase of monoamine oxidase B in amyloid-negative cognitively unimpaired elderly subjects. Ann Nucl Med 36, 777–784 (2022). https://doi.org/10.1007/s12149-022-01760-6

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  • DOI: https://doi.org/10.1007/s12149-022-01760-6

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