Granholm Neurodegeneration Lab

My lab is focused on mechanisms associated with neurodegeneration, in particular Down syndrome (DS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). To study the mechanisms for these severe conditions, we utilize both mouse models and human tissues, as well as studying biomarkers in human plasma. The DS project is focused on early biomarkers associated with development of AD in those with Down syndrome. Pathology for AD develops early in life in those with DS, and mechanisms leading to this are not fully known. To make tissues more available for study, I started a consortium of brain banks focusing on DS and this consortium now has 11 sites in 5 countries. This brain bank is supported by the BrightFocus foundation and the Lejeune Foundation as well as an R01 grant from the National Institutes on Aging. In particular, we are focusing on mechanisms for an early onset of Tau pathology in DS and investigating exosome-related biomarkers from both brain tissue and plasma.

Another project in the lab is focused on PD. We are collaborating with a research group in the Department of Neurosurgery at University of Kentucky on examining the effects of intracranial autografts of sural nerve tissue in patients with either AD or PD. It is known that peripheral nerves have an inherent ability to regenerate, contrary to nerves in the brain. We are utilizing this regenerative ability with significant clinical results. The Granholm group is focused on examining the postmortem pathology of patients with PD, AD, and sural nerve grafts. This project was recently funded by an R01 grant from the National Institutes on Aging (NIA).

Finally, I have an R01 from the NIA focused on AD biomarkers for mild traumatic brain injury (mTBI) or concussion in Division 1 athletes. We are following a large cohort of athletes at University of Denver with baseline examination of plasma biomarkers, balance, and cognitive performance as well as the same clinical assessments at different time periods after a concussion. This project has been going on since 2016, and we have hundreds of athletes in the cohort. Preliminary findings in this project suggest that impulse control and reaction times are affected long-term following a concussion, despite the return-to-play which usually occurs a couple of weeks after the injury.

About the Teammates

Ann-Charlotte Granholm-Bentley, PhD/DDS: Lotta is a Professor in Department of Neurosurgery and a native of Sweden. She first came to CU as a postdoc in 1985 and returned to CU in 2021 after long stints at Medical University of South Carolina (MUSC) and University of Denver. She has a background in histology and has lately focused mostly on neuropathology of neurodegenerative disorders. 

Campbell Pontin, B.S.: Campbell is a recent Biology graduate from the University of Colorado Denver. Her current projects in the lab include investigating the effects of trisomic human exosome injections into mouse brains, and expanding on previous student research on the interactions between Down Syndrome, COVID and Alzheimer’s disease in the human brain. Outside of work, Campbell spends her time snowboarding, hiking, gardening, going to concerts, and adventuring with her two dogs, Bluebell and Scoby. 

Jeremiah Phares B.S.: I am the lab manger in Dr. Granholm’s lab. I graduated from Metropolitan State University of Denver with degrees in Biology and Psychology. My interests include neurodegeneration, brain-machine interface, prosthetics, exercise physiology, healthy aging, and behavior. My projects are autologous grafts in Parkinson’s disease and utilizing spatial transcriptomics and other ‘omics methods to understand the mechanisms of Alzheimer’s Disease in individuals with Down Syndrome. 

Abigail Wohlfert, B.S: Abby is a graduate student in the Department of Cell and Developmental Biology, working towards a Master’s of Science in Modern Human Anatomy. She is a Michigan native and went to Alma College in Alma, MI where she obtained a Bachelor’s of Science in Integrative Physiology and Health Science. Abby is currently studying the mTOR pathway in relation to DS-AD in the Granholm lab and hopes to receive a PhD in neuroscience one day. 

RECENT PUBLICATIONS:

Granholm AC, Englund E, Gilmore A, Head E, Yong WH, Perez SE, Guzman SJ, Hamlett ED, Mufson EJ. Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2: preliminary findings. Acta Neuropathol. 2024 May 27;147(1):92. doi: 10.1007/s00401-024-02743-9. PMID: 38801558; PMCID: PMC11130011. Impact factor: 12.7.

Granholm AC, Hamlett ED. The Role of Tau Pathology in Alzheimer's Disease and Down Syndrome. J Clin Med. 2024 Feb 27;13(5):1338. doi: 10.3390/jcm13051338. PMID: 38592182; PMCID: PMC10932364.

Aldecoa I, Barroeta I, Carroll SL, Fortea J, Gilmore A, Ginsberg SD, Guzman SJ, Hamlett ED, Head E, Perez SE, Potter H, Molina-Porcel L, Raha-Chowdhury R, Wisniewski T, Yong WH, Zaman S, Ghosh S, Mufson EJ, Granholm AC. Down Syndrome Biobank Consortium: A perspective. Alzheimers Dement. 2024 Mar;20(3):2262-2272. doi: 10.1002/alz.13692. Epub 2024 Jan 25. PMID: 38270275; PMCID: PMC10984425. Impact factor: 16.6.

Colvett I, Gilmore A, Guzman S, Ledreux A, Quintero JE, Ginjupally DR, Gurwell JA, Slevin JT, Guduru Z, Gerhardt GA, van Horne CG, Granholm AC. Recipient Reaction and Composition of Autologous Sural Nerve Tissue Grafts into the Human Brain. J Clin Med. 2023 Sep 22;12(19):6121. doi: 10.3390/jcm12196121. PMID: 37834764; PMCID: PMC10573749.

Granholm AC, Ledreux A. Biomarkers show value of studying dementia in Down syndrome. Nat Rev Neurol. 2021 Oct;17(10):599-600. doi: 10.1038/s41582-021-00558-w. PMID: 34465922; PMCID: PMC11353155. Impact factor: 44.7.