Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer’s disease mouse model

Molecular Psychiatry volume 26, pages 5669–5689 (2021)Cite this article

Subjects

Abstract

Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN−/−) mice developed Alzheimer’s like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased Aβ-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer’s disease (AD) pathogenesis. Here, we demonstrated that APN levels were reduced in the brain of AD patients and 5xFAD mice. We crossbred 5xFAD mice with APN−/− mice to generate APN-deficient 5xFAD (5xFAD;APN−/−). APN deficiency in 5xFAD mice accelerated amyloid loading, increased cerebral amyloid angiopathy, and reduced insulin-signaling activities. Pharmacokinetics study demonstrated adipoRon (APN receptor agonist) was a blood–brain barrier penetrant. AdipoRon improved neuronal insulin-signaling activities and insulin sensitivity in vitro and in vivo. Chronic adipoRon treatment improved spatial memory functions and significantly rescued neuronal and synaptic loss in 5xFAD and 5xFAD;APN−/− mice. AdipoRon lowered plaque and Aβ levels in AD mice. AdipoRon also exerted anti-inflammatory effects by reducing microglial and astrocytes activation as well as suppressing cerebral cytokines levels. The microglial phagocytic activity toward Aβ was restored after adipoRon treatment. Our results indicated that adipoRon exerts multiple beneficial effects providing important therapeutic implications. We propose chronic adipoRon administration as a potential treatment for AD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: APN deficiency in human AD brain tissues and AD mouse model.
Fig. 2: Deficiency of adiponectin leads to more severe memory decline and neuropathology.
Fig. 3: AdipoRon crosses blood–brain barrier and enhances insulin sensitivity and ameliorates insulin resistance in AD mouse model.
Fig. 4: AdipoRon improves cognitive functions and restores neuronal and synaptic densities in AD mouse model.
Fig. 5: AdipoRon reduces amyloid pathology in the 9-month old AD mouse models.
Fig. 6: AdipoRon reduces microgliosis, astrogliosis, and neuroinflammatory responses in 9-month old AD mouse models.

Similar content being viewed by others

References

  1. Zahs KR, Ashe KH. β-Amyloid oligomers in aging and alzheimer’s disease. Front Aging Neurosci. 2013;5:1–5.

    Google Scholar 

  2. Takeda S, Sato N, Uchio-Yamada K, Sawada K, Kunieda T, Takeuchi D, et al. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci USA. 2010;107:7036–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Yarchoan M, Toledo JB, Lee EB, Arvanitakis Z, Kazi H, Han LY. et al. Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer’s disease and tauopathies. Acta Neuropathol. 2014;128:679–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Talbot K, Wang H, Kazi H, Han L, Bakshi KP, Stucky A, et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is assocaited with IGF-1 resisitance, IRS-1 dysregulation, and cogntive decline. J Clin Investig. 2012;122:1316–38.

  5. DaRocha-Souto B, Coma M, Pérez-Nievas BG, Scotton TC, Siao M, Sánchez-Ferrer P, et al. Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in Alzheimer’s disease. Neurobiol Dis. 2012;45:425–37.

    CAS  PubMed  Google Scholar 

  6. Ly PTT, Wu Y, Zou H, Wang R, Zhou W, Kinoshita A, et al. Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes. J Clin Investig. 2013;123:224–35.

    CAS  PubMed  Google Scholar 

  7. Rodríguez M, Clarimón J, Gich I, Sánchez-Ferrer P, Serenó L, Lleó A, et al. A novel GSK-3β inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009;35:359–67.

    PubMed  Google Scholar 

  8. Bomfim TR, Forny-germano L, Sathler LB, Brito-moreira J, Houzel J, Decker H, et al. An anti-diabetes agent protects the mousebrain from defective insulin signalingcaused by Alzheimer’s disease–associated Aβ oligomers. J Clin Investig. 2012;122:1339–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kondo H, Shimomura L, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002;51:2325–8.

    CAS  PubMed  Google Scholar 

  10. Ng RCL, Chan KH. Potential neuroprotective effects of adiponectin in Alzheimer’s disease. Int J Mol Sci. 2017;18:1–13.

    Google Scholar 

  11. Une K, Takei Ya, Tomita N, Asamura T, Ohrui T, Furukawa K, et al. Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer’s disease. Eur J Neurol. 2011;18:1006–9.

    CAS  PubMed  Google Scholar 

  12. Teixeira AL, Diniz BS, Campos AC, Miranda AS, Rocha NP, Talib LL, et al. Decreased levels of circulating adiponectin in mild cognitive impairment and alzheimer’s disease. NeuroMolecular Med. 2013;15:115–21.

    CAS  PubMed  Google Scholar 

  13. García-Casares N, García-Arnés JA, Rioja J, Ariza MJ, Gutiérrez A, Alfaro F, et al. Alzheimer’s like brain changes correlate with low adiponectin plasma levels in type 2 diabetic patients. J Diabetes Complicat. 2016;30:281–6.

    Google Scholar 

  14. Himbergen TM van, Alexa SB, Ai M, Seshadri S, Otokozawa S, Au R. et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease results from the Framingham Heart Study. Arch Neurol. 2012;69:564–600.

    Google Scholar 

  15. Waragai M, Adame A, Trinh I, Sekiyama K, Takamatsu Y, Une K, et al. Possible Involvement of adiponectin, the anti-diabetes molecule, in the pathogenesis of Alzheimer’s disease. J Alzheimer’s Dis. 2016;52:1453–9.

    CAS  Google Scholar 

  16. Ng RC-L, Cheng OY, Kwan JSC, Ho PWL, Cheng KKY, Yeung PKK, et al. Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments through AMPK inactivation and cerebral insulin resistance in aged mice. Mol Neurodegener. 2016;11:1–16.

    Google Scholar 

  17. Jian M, Kwan JSC, Bunting M, Ng RCL, Chan KH. Adiponectin suppresses amyloid-β oligomer (AβO)-induced inflammatory response of microglia via AdipoR1-AMPK-NF-κB signaling pathway. J Neuroinflammation. 2019;16:1–19.

    CAS  Google Scholar 

  18. Kim MW, Abid N, bin, Jo MH, Jo MG, Yoon GH, Kim MO. Suppression of adiponectin receptor 1 promotes memory dysfunction and Alzheimer’s disease-like pathologies. Sci Rep. 2017;7:12435.

    PubMed  PubMed Central  Google Scholar 

  19. Zhang D, Wang X, Wang B, Garza JC, Fang X, Wang J, et al. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors. Mol Psychiatry. 2017;22:1044–55.

    CAS  PubMed  Google Scholar 

  20. Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013;503:493–9.

    CAS  PubMed  Google Scholar 

  21. Gay A-S, Maroteaux L, Heurteaux C, Chabry J, Bayer P, Béchade C, et al. Adiporon, an adiponectin receptor agonist acts as an antidepressant and metabolic regulator in a mouse model of depression. Transl Psychiatry. 2018;8:159.

  22. Patel H, Hodges AK, Curtis C, Lee SH, Troakes C, Dobson RJB, et al. Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains. Brain Behav Immun. 2019;80:644–56.

    PubMed  Google Scholar 

  23. Chu LW, Shea YF, Ha J. Validation of AD-CSF-Index in Chinese patients with Alzheimer’s disease and nondemented controls. Am J Alzheimers Dis Other Demen. 2015;30:522–6.

    PubMed  Google Scholar 

  24. Schumann-Bard P, Leger M, Quiedeville A, Bouet V, Boulouard M, Freret T, et al. Object recognition test in mice. Nat Protoc. 2013;8:2531–7.

    PubMed  Google Scholar 

  25. Oliveira VC, Carrara RCV, Simoes DLC, Saggioro FP, Carlotti CG, Covas DT, et al. Sudan black B treatment reduces autofluorescence and improves resolution of in situhybridization specific fluorescent signals of brain sections. Histol Histopathol. 2010;25:1017–24.

    CAS  PubMed  Google Scholar 

  26. Chan KH, Lam KSL, Cheng OY, Kwan JSC, Ho PWL, Cheng KKY, et al. Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity. PLoS ONE. 2012;7:e52354.

  27. Lian H, Roy E, Zheng H. Microglial phagocytosis assay. Bio-Protocols. 2016;6:1–12.

    Google Scholar 

  28. Eimer Wa, Vassar R. Neuron loss in the 5XFAD mouse model of Alzheimer’s disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation. Mol Neurodegener. 2013;8:2.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Marschner A, Vervliet B, Kalisch R, Buchel C, Vansteenwegen D. Dissociable roles for the hippocampus and the amygdala in human cued versus context fear conditioning. J Neurosci. 2008;28:9030–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ma T, Hoeffer CA, Wong H, Massaad CA, Zhou P, Iadecola C, et al. Amyloid beta-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide. J Neurosci. 2011;31:5589–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Grillo C, Piroli G, Lawrence R, Wrighten S, Green A, Wilson S, et al. Hippocampal insulin resistance impairs spatial learning and synaptic plasticity. Diabetes. 2015;64:3927–36.

  32. Minami SS, Min S-W, Krabbe G, Wang C, Zhou Y, Asgarov R, et al. Progranulin protects against amyloid β deposition and toxicity in Alzheimer’s disease mouse models. Nat Med. 2014;20:1157–64.

  33. Hu S, Begum AN, Jones MR, Oh MS, Beech WK, Beech BH, et al. GSK3 inhibitors show benefits in an Alzheimer’s disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis. 2009;33:193–206.

    CAS  PubMed  Google Scholar 

  34. Chen CH, Zhou W, Liu S, Deng Y, Cai F, Tone M, et al. Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer’s disease. Int J Neuropsychopharmacol. 2012;15:77–90.

    CAS  PubMed  Google Scholar 

  35. Bates KA, Verdile G, Li QX, Ames D, Hudson P, Masters CL, et al. Clearance mechanisms of Alzheimer’s amyloid-Β peptide: Implications for therapeutic design and diagnostic tests. Mol Psychiatry. 2009;14:469–86.

    CAS  PubMed  Google Scholar 

  36. Carpentier M, Robitaille Y, DesGroseillers L, Boileau G, Marcinkiewicz M. Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002;61:849–56.

    CAS  PubMed  Google Scholar 

  37. Pérez A, Morelli L, Cresto JC, M. CE. Degradation of soluble amyloid beta-peptides 1–40, 1–42, and the Dutch variant 1–40Q by insulin degrading enzyme from Alzheimer disease and control brains. Neurochem Res. 2000;25:247–55.

    PubMed  Google Scholar 

  38. Stanley M, Macauley SL, Holtzman DM. Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence? J Exp Med. 2016;213:jem.20160493.

    Google Scholar 

  39. Masaki T, Anan F, Shimomura T, Fujiki M, Saikawa T, Yoshimatsu H. Association between hippocampal volume and serum adiponectin in patients with type 2 diabetes mellitus. Metabolism. 2012;61:1197–200.

    CAS  PubMed  Google Scholar 

  40. Cisternas P, Martinez M, Ahima RS, William WG, Inestrosa NC. Modulation of glucose metabolism in hippocampal neurons by adiponectin and resistin. Mol Neurobiol. 2018. https://doi.org/10.1007/s12035-018-1271-x.

  41. Heneka MT, Fink A, Doblhammer G. Effect of pioglitazone medication on the incidence of dementia. Ann Neurol. 2015;78:284–94.

    CAS  PubMed  Google Scholar 

  42. Hsieh C-Y, Lu C-H, Yang C-Y, Ou H-T, Li C-Y. Lower risk of dementia with pioglitazone, compared with other second-line treatments, in metformin-based dual therapy: a population-based longitudinal study. Diabetologia. 2017;61:562–73.

    PubMed  Google Scholar 

  43. Forny-Germano L, De Felice FG, Vieira MN, do N. The role of leptin and adiponectin in obesity-associated cognitive decline and Alzheimer’s disease. Front Neurosci. 2019;12:1–19.

    Google Scholar 

  44. Shah SA, Yoon GH, Chung SS, Abid MN, Kim TH, Lee HY, et al. Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol Psychiatry. 2017;22:407–16.

    CAS  PubMed  Google Scholar 

  45. Song J, Choi SM, Whitcomb DJ, Kim BC. Adiponectin controls the apoptosis and the expression of tight junction proteins in brain endothelial cells through AdipoR1 under beta amyloid toxicity. Cell Death Dis. 2017;8:1–13.

    Google Scholar 

  46. Kalaria RN. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease. Acta Neuropathol. 2016;131:659–85.

    PubMed  PubMed Central  Google Scholar 

  47. Charlton A, Smith EE, Hogan DB, Haffenden A, Batool S, Goodyear B, et al. Cerebral amyloid angiopathy is associated with executive dysfunction and mild cognitive impairment. Stroke. 2016;47:2010–6.

    PubMed  Google Scholar 

  48. Guyon A, Petit-Paitel A, Cazareth J, Zarif H, Chabry J, Heurteaux C, et al. Globular adiponectin limits microglia pro-inflammatory phenotype through an AdipoR1/NF-κB signaling pathway. Front Cell Neurosci. 2017;11:352.

  49. Song J, Choi S-M, Kim BC. Adiponectin regulates the polarization and function of microglia via PPAR-γ signaling under amyloid β toxicity. Front Cell Neurosci. 2017;11:64.

  50. Min J, Ng RC-L, Chan K-H. Adiponectin suppresses amyloid-β (Aβ)-induced neuroinflammation in Alzheimer’s disease via AMPK-NF-kB singaling pathway. Soc Neurosci. 2017;126:19.

  51. Price Ka, Varghese M, Sowa A, Yuk F, Brautigam H, Ehrlich ME, et al. Altered synaptic structure in the hippocampus in a mouse model of Alzheimer’s disease with soluble amyloid-β oligomers and no plaque pathology. Mol Neurodegener. 2014;9:41.

    PubMed  PubMed Central  Google Scholar 

  52. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1:1–23.

    Google Scholar 

  53. Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML, Garcia-Alloza M, et al. Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci USA. 2009;106:4012–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Mishra A, Kim HJ, Shin AH, Thayer SA. Synapse loss induced by interleukin-1β requires pre-and post-synaptic mechanisms. J Neuroimmune Pharmacol. 2012;7:571–8.

    PubMed  PubMed Central  Google Scholar 

  55. Parajuli B, Sonobe Y, Horiuchi H, Takeuchi H, Mizuno T, Suzumura A. Oligomeric amyloid β induces IL-1β processing via production of ROS: implication in Alzheimer’s disease. Cell Death Dis. 2013;4:1–8.

    Google Scholar 

  56. Kokiko-Cochran ON, Weick JP, Xu G, Ransohoff RM, Staugaitis SM, Lamb BT, et al. Microglial derived tumor necrosis factor-α drives Alzheimer’s disease-related neuronal cell cycle events. Neurobiol Dis. 2013;62:273–85.

    PubMed  Google Scholar 

  57. Zhang D, Wang X, Lu XY. Adiponectin exerts neurotrophic effects on dendritic arborization, spinogenesis, and neurogenesis of the dentate gyrus of male mice. Endocrinology. 2016;157:2853–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Yau S-Y, Li A, Hoo RLC, Ching YP, Christie BR, Lee TMC, et al. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Proc Natl Acad Sci USA. 2014;111:15810–5.

  59. Liu J, Guo M, Zhang D, Cheng S-Y, Liu M, Ding J, et al. Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity. Proc Natl Acad Sci USA. 2012;109:12248–53.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Prof. Kiren Rockenstein (Salk Institute) in sharing the immortalized mouse hippocampal HT-22 neuronal cell line. We also thank the technical staffs in the Faculty Core Facility, HKU, in assisting the confocal microscopy and IMARIS software operation. We are also grateful to the Brain Bank, NIHR BRC at Imperial College and Alzheimer’s Research, to provide human paraffin sections and human CSF. This work was supported by grants to RC-LN from the Health & Medical Research Fund (ref no. 03143856) and Chan Kin Shing Charitable Trust to K-HC. This work was also partly supported by grants to ML from the Hong Kong General Research Fund (GRF/HKBU12101417, GRF/HKBU12100618) and the Health & Medical Research Fund (HMRF/15163481, HMRF14150811). This work was also partly supported by grants to S-SKD from the Hong Kong Innovation Technology Fund (ITS/253/14).

Author information

Authors and Affiliations

  1. Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

    Roy Chun-Laam Ng, Min Jian, Oscar Ka-Fai Ma, Myriam Bunting, Jason Shing-Cheong Kwan, Karen Siu-Ling Lam, Leung-Wing Chu & Koon-Ho Chan

  2. Neuroimmunology and Neuroinflammation Research Laboratory, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

    Roy Chun-Laam Ng, Min Jian, Oscar Ka-Fai Ma, Myriam Bunting, Jason Shing-Cheong Kwan & Koon-Ho Chan

  3. The Swire Institute of Marine Science and School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China

    Guang-Jie Zhou & Kenneth Mei-Yee Leung

  4. Mr & Mrs Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China

    Krishnamoorthi Senthilkumar, Ashok Iyaswamy, Min Li & Siva-Sundara Kumar Durairajan

  5. Gene Control Mechanisms and Disease Group, Department of Brain Sciences, Faculty of Medicine, MRC London Institute of Medical Sciences, Imperial College London, London, W120NN, UK

    Ping-Kei Chan & Richard Festenstein

  6. Division of Myobiology and Neurodegenerative Disease Research, Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, India

    Siva-Sundara Kumar Durairajan

  7. Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Pokfulam, Hong Kong, China

    Karen Siu-Ling Lam, Sookja Kim Chung & Koon-Ho Chan

  8. School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

    Sookja Kim Chung

  9. Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau

    Sookja Kim Chung

Authors
  1. Roy Chun-Laam Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Jian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oscar Ka-Fai Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Myriam Bunting
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jason Shing-Cheong Kwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guang-Jie Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Krishnamoorthi Senthilkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ashok Iyaswamy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ping-Kei Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kenneth Mei-Yee Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Siva-Sundara Kumar Durairajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Karen Siu-Ling Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Leung-Wing Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Richard Festenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sookja Kim Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Koon-Ho Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Koon-Ho Chan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ng, R.CL., Jian, M., Ma, O.KF. et al. Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer’s disease mouse model. Mol Psychiatry 26, 5669–5689 (2021). https://doi.org/10.1038/s41380-020-0701-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-020-0701-0

This article is cited by

Search

Advanced search

Quick links