John D. Fryer, Ph.D.

Associate Professor of Neuroscience, Mayo Clinic Arizona

Dr. Fryer’s lab is focused on understanding the cellular and molecular mechanisms of Alzheimer’s disease (AD) pathogenesis. During his graduate studies in the lab of Dr. David M. Holtzman, MD at Washington University in St. Louis, he elucidated the role of apolipoprotein E (apoE) in the formation of amyloid in the cerebrovasculature, termed cerebral amyloid angiopathy, a pathology that occurs in the majority of Alzheimer’s cases and can lead to fatal hemorrhages. For his postdoctoral work, Dr. Fryer joined the lab of Dr. Huda Y. Zoghbi, MD at Baylor College of Medicine (Houston, TX), where he studied detailed molecular mechanisms of underlying spinocerebellar ataxia type 1, a severe neurodegenerative disease due to a polyglutamine repeat expansion. Upon his recruitment to Mayo Clinic in 2011, he returned to the Alzheimer’s field and has focused on studying the role of the immune system in Alzheimer’s disease pathogenesis as well as the role of other AD genes such as Clusterin (CLU), also known as apolipoprotein J (apoJ). His lab published an unexpected role of CLU in the formation of cerebral amyloid angiopathy, but his recent work indicates that CLU also plays a role tau pathology. ApoE was recently shown to play a role in not only amyloid but also tau pathology, and CLU also seems to be another apolipoprotein that plays a role in this process. He continues to use mouse models and human tissue samples to study how CLU is impacting AD and hopes this understanding will lead to new therapeutic approaches to halt or slow the progression of AD pathology.

Related Research:

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
The Role of Clusterin in Tau Pathology 2019, 2021


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Liu, C. C., Murray, M. E., Li, X., Zhao, N., Wang, N., Heckman, M. G., Shue, F., Martens, Y., Li, Y., Raulin, A. C., Rosenberg, C. L., Doss, S. V., Zhao, J., Wren, M. C., Jia, L., Ren, Y., Ikezu, T. C., Lu, W., Fu, Y., Caulfield, T., Trottier, Z.A., Knight, J., Chen, Y., Linares, C., Wang, X., Kurti, A., Asmann, Y.W., Wszolek, Z.K., Smith, G.E., Vemuri, P., Kantarci, K., Knopman, D.S., Lowe, V.J., Jack, C.R. Jr, Parisi, J.E., Ferman, T.J., Boeve, B.F., Graff-Radford, N.R., Petersen, R.C., Younkin, S.G., Fryer, J.D., Wang, H., Han, X., Frieden, C., Dickson, D.W., Ross, O.A., Bu, G. APOE3-Jacksonville (V236E) variant reduces self-aggregation and risk of dementia, Science Translational Medicine, September 29, 2021, Read More

Liu, C. C., Zhao, J., Fu, Y., … Kanekiyo, T., Fryer, J. D., … Bu, G. Peripheral apoE4 enhances Alzheimer’s pathology and impairs cognition by compromising cerebrovascular function, Nature Neuroscience, August 1, 2022, Read More

Cadiz, M. P., Jensen, T. D., Sens, J. P., Zhu, K., Song, W. M., Zhang, B., Ebbert, M., Chang, R., & Fryer, J. D. Culture shock: microglial heterogeneity, activation, and disrupted single-cell microglial networks in vitro, Molecular Neurodegeneration, March 28, 2022, Read More

Olney, K. C., Todd, K. T., Pallegar, P. N., Jensen, T. D., Cadiz, M. P., Gibson, K. A., Barnett, J. H., de Ávila, C., Bouchal, S. M., Rabichow, B. E., Ding, Z., Wojtas, A. M., Wilson, M. A., & Fryer, J. D. Widespread choroid plexus contamination in sampling and profiling of brain tissue, Molecular Psychiatry, January 5, 2022, Read More

Shinohara, M., Kanekiyo, T., Tachibana, M., Kurti, A., Shinohara, M., Fu, Y., Zhao, J., Han, X., Sullivan, P. M., Rebeck, G. W., Fryer, J. D., Heckman, M. G., & Bu, G. APOE2 is associated with longevity independent of Alzheimer’s disease, eLife, October 19, 2020, Read More

Wojtas, A. M., Carlomagno, Y., Sens, J. P., Kang, S. S., Jensen, T. D., Kurti, A., Baker, K. E., Berry, T. J., Phillips, V. R., Castanedes, M. C., Awan, A., DeTure, M., De Castro, C. H. F., Librero, A. L., Yue, M., Daughrity, L., Jansen-West, K. R., Cook, C. N., Dickson, D. W., Petrucelli, L., Fryer, J. D. Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation, Acta Neuropathologica Communications, December 1, 2020, Read More

Wojtas, A. M., Sens, J. P., Kang, S. S., Baker, K. E., Berry, T. J., Kurti, A., Daughrity, L., Jansen-West, K. R., Dickson, D. W., Petrucelli, L., Bu, G., Liu, C. C., & Fryer, J. D. Astrocyte-derived clusterin suppresses amyloid formation in vivo, Molecular Neurodegeneration, November 27, 2020, Read More

Yamazaki, Y., Liu, C. C., Yamazaki, A., Shue, F., Martens, Y. A., Chen, Y., Qiao, W., Kurti, A., Oue, H., Ren, Y., Li, Y., Aikawa, T., Cherukuri, Y., Fryer, J. D., Asmann, Y. W., Kim, B. Y. S., Kanekiyo, T., & Bu, G. Vascular ApoE4 Impairs Behavior by Modulating Gliovascular Function, Neuron, December 14, 2020, Read More

Liu, C. C., Wang, N., Chen, Y., Inoue, Y., … Fryer, J. D., … Bu, G. Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer’s disease, Nature Immunology, October 19, 2023, Read More

Painter, M. M., Atagi, Y., Liu, C. C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. TREM2 in CNS homeostasis and neurodegenerative disease, Molecular Neurodegeneration, September 4, 2015, Read More

Cadiz, M. P., Gibson, K. A., Todd, K. T., Nascari, D. G., Massa, N., Lilley, M. T., Olney, K. C., Al-Amin, M. M., Jiang, H., Holtzman, D. M., & Fryer, J. D. Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations, Journal of Experimental Medicine, January 16, 2024, Read More

Olney, K. C., de Ávila, C., Todd, K. T., Tallant, L. E., Barnett, J. H., Gibson, K. A., Hota, P., Pandiane, A. S., Durgun, P. C., Serhan, M., Wang, R., Lind, M. L., Forzani, E., Gades, N. M., Thomas, L. F., & Fryer, J. D. Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia, Journal of Neuroinflammation, January 4, 2024, Read More