Room 311, Sanders-Brown Center On Aging
800 South Limestone Street
Lexington, KY 40536-0230
Pathology, Division of Neuropathology
Non-coding RNA in neurodegenerative disease
(left to right) Pete Nelson, James Dimayuga, Bernard R. Wilfred, Wang-Xia Wang, Mary Jennings, Kevin Xie, Willa Huang, Guogen Mao
Work on RNA biology may help point toward strategies to 'un-tangle' the biological questions of Alzheimer's disease, such as why neuritic plaques and neurofibrillary tangles develop in the brains of Alzheimer's patients. (lower left figure shows a low-power photomicrograph depicting miRNA in situ hybridization from human hippocampus; and, at lower right, a medium-power photomicrograph shows human brain stained with a silver impregnation technique to highlight the abnormal and unhealthy-appearing brain microenvironment).
Dr. Pete Nelson is an experimental neuropathologist focusing on Alzheimer’s disease. Dr Nelson is the Director of the Neuropathology Division of the Pathology Department, and he also directs the brain bank and the Neuropathology Core of the University of Kentucky Alzheimer’s Disease Center. Dr. Nelson is responsible for the Alzheimer’s Disease Center brain autopsies. These autopsies are performed with profound respect for the volunteers who are enabling us to help combat this dreadful disease. Dr. Nelson’s career is motivated partly by his own grandmother, Sylvia “Tib” Becker, who died with Alzheimer's disease.
In addition to duties as a neuropathologist, Dr. Nelson is an experimental researcher focusing on the molecular neurochemistry of the human brain — in health and in neurodegenerative disease — particularly in the context of RNA biology. The study of small regulatory RNAs is a relatively new and unexplored research field with much potential. Dr. Nelson's work has focused upon microRNAs (miRNAs). He invented new techniques to analyze and manipulate these small molecules, and studies how miRNA biology is altered in neurodegenerative diseases. Dr. Nelson seeks both to understand how miRNAs contribute to disease pathogenesis, and to explore how specially-designed RNAs may be applied for therapeutic strategies.
Nelson, PT*, Schmitt, FA, Lin, Y, Abner, EL, Jicha, GA, Patel, E, Thomason, PC, Neltner, JH, Smith, CD, Santacruz, KS, Sonnen, JA, Poon, LW, Gearing, M, Green, RC, Woodard, JL, Van Eldik, LJ, Kryscio, RJ. Hippocampal sclerosis in advanced age: clinical and pathological features in 106 cases "Brain 134: 1506-1518 (2011)".
Abner, EL, Kryscio, RJ, Schmitt, FA, Santacruz, KS, Jicha, GA, Lin, Y, Neltner JH, Smith, CD, Van Eldik, LJ, Nelson, PT*, “End-stage” neurofibrillary tangle pathology in preclinical Alzheimer’s disease—fact or fiction?, J Alzheimer's Disease, In Press 2011
Jicha, GA, Abner EL, Schmitt, FA, Kryscio, RJ, Riley, KP, Cooper, GE, Stiles, JN, Mendiondo, MS, Smith CD, Van Eldik, LJ, and Nelson, PT*, Preclinical AD Workgroup staging: pathological correlates and potential challenges, Neurobiology of Aging, In Press 2011
Jicha, GA and Nelson, PT, Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options, Neurodegen Dis Management, In Press 2011
Riley, KP, Jicha, GA, Davis, D, Abner, EL, Cooper, GE, Stiles, N, Smith, CD, Kryscio, RJ, Nelson, PT, Van Eldik LJ, and Schmitt, FA, Prediction of preclinical Alzheimer’s disease: Longitudinal rates of change in cognition, J Alzheimer's Disease, In Press 2011
Niedowicz DM, Nelson PT, Murphy MP. Alzheimer’s Disease: Pathological Mechanisms and Recent Insights Curr Neuropharmacol In Press 2010
Madathil SK, Nelson PT*, Saatman KE, Wilfred BR, MicroRNAs in CNS injury: potential roles and therapeutic implications, Bioessays, In Press 2010
Wang WX, Huang Q, Hu Y, Stromberg AJ, Nelson PT*. Patterns of microRNA expression in normal and early Alzheimer's disease human temporal cortex: white matter versus gray matter. Acta Neuropathol. 2010 Oct 10.
Wang WX, Kyprianou N, Wang X, Nelson PT*. Dysregulation of the mitogen granulin in human cancer through the miR-15/107 microRNA gene group. Cancer Res. 2010 Sep 30.
Finnerty JR, Wang WX, Hébert SS, Wilfred BR, Mao G, Nelson PT*. The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases. J Mol Biol. 2010 Sep 24;402(3):491-509.
Nelson PT*, Schmitt FA, Jicha GA, Kryscio RJ, Abner EL, Smith CD, Van Eldik LJ, Markesbery WR. Association between male gender and cortical Lewy body pathology in large autopsy series. J Neurol. 2010
Wang WX, Wilfred BR, Madathil SK, Tang G, Hu Y, Dimayuga J, Stromberg AJ, Huang Q, Saatman KE, Nelson PT*. miR-107 regulates granulin/progranulin with implications for traumatic brain injury and neurodegenerative disease. Am J Pathol. 2010 Jul;177(1):334-45.
Wang WX, Wilfred BR, Xie K, Jennings MH, Hu Y, Stromberg AJ, Nelson PT*. Individual microRNAs (miRNAs) display distinct mRNA targeting "rules" RNA Biol. 2010 May 5;7(3).
Nelson PT*, Kukull WA, Frosch MP. Thinking outside the box: Alzheimer-type neuropathology that does not map directly onto current consensus recommendations. JNEN. 2010 May;69(5):449-54
Nelson PT*, Wang WX. MiR-107 is Reduced in Alzheimer's Disease Brain Neocortex: Validation Study. J Alzheimers Dis. 2010
Nelson PT*, Kiriakidou M, Mourelatos Z, Tan GS, Jennings MH, Xie K, Wang WX. High-throughput experimental studies to identify miRNA targets directly, with special focus on the mammalian brain. Brain Res. 2010 Jun 18;1338:122-30.
Balamuthia mandrillaris meningoencephalitis: survival of a pediatric patient. Cary LC, Maul E, Potter C, Wong P, Nelson PT, Given C 2nd, Robertson W Jr. Pediatrics. 2010 Mar;125(3):e699-703.
Nelson PT*, Dimayuga J, Wilfred, BR, MicroRNA in situ hybridization in the human entorhinal and transentorhinal cortex. Front Hum Neurosci, 2010
Wang W-X, Wilfred BR, Hu Y, Stromberg AJ, Nelson PT*, Argonaute co-immunoprecipitation with RIP-CHIP show that miRNA transfection alter global patterns of mRNA recruitment to microribonucleoprotein complexes. RNA, 2010.
Nelson PT*, Jicha GA, Kryscio RJ, Abner EL, Schmitt FA, Cooper G, Xu LO, Smith CD, Markesbery WR. Low sensitivity in clinical diagnoses of dementia with Lewy bodies. J Neurol. 2009 Oct 1.
Nelson, PT*, Kryscio, RJ, Jicha, GA, Abner, EL, Schmitt, FA, Xu, L, Cooper, G, Smith, CD, Markesbery, WR, Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies, Neurology (2009)
Nelson, PT*, Kryscio, RJ, Jicha, GA, Abner, EL, Schmitt, FA, Xu, L, Cooper, G, Smith, CD, Markesbery, WR, Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. J Neuropathol Exp Neurol. 2009 Jul;68(7):774-84
Berger JR, Fee DB, Nelson P, Nuovo G. Coxsackie B meningoencephalitis in a patient with acquired immunodeficiency syndrome and a multiple sclerosis-like illness. J Neurovirol. 2009 May 14:1-6.
Berger JR, Dillon DA, Young BA, Goldstein SJ, Nelson P Cystinosis of the brain and spinal cord with associated vasculopathy. J Neurol Sci. 2009 Sep 15;284(1-2):182-5. Epub 2009 Apr 22.
Nelson PT*, Wilfred BR. In situ hybridization is a necessary experimental complement to microRNA (miRNA) expression profiling in the human brain. Neurosci Lett. 2009 Apr 23.
Nelson PT*, Abner, EA, Scheff, SW, Schmitt, FA, Kryscio, RJ, Jicha, GA, Smith, CD, Patel, E, Markesbery, WR, Alzheimer pathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment. Neurosci Letters, 2009.
Nelson PT*, Braak H, and Markesbery WR, Neuropathology and Cognitive Impairment in Alzheimer’s Disease: A Complex but Coherent Relationship. J Neuropathol Exp Neurol. 2009 Jan;68(1):1-14.
Nelson PT*, Abner, EA, Schmitt, FA, Kryscio, RJ, Jicha, GA, Smith, CD, Davis, DG, Poduska, JW, Patel, E, Mendiondo, MS, Markesbery, WR, Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol, (2008).
Jicha, GA, Schmitt, FA, Abner, EL, Nelson, PT, Cooper, GE, Smith, CD, and Markesbery, WR, Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiol Aging, 2008
Nelson PT*, Smith, CD, Abner, EA, Schmitt, FA, Scheff, SW, Davis, GD, Keller, JN, Jicha, GA, Davis, D, Wang, W-X, Hartman, A, Katz, DG, and Markesbery WR, Human cerebral neuropathology of Type 2 diabetes mellitus. BBA-Mol Basis of Disease, 2008
Nelson PT*, Kryscio, RJ, Abner, EA, Schmitt, FA, Jicha, GA, Mendiondo, MS, Cooper, G, Smith, CB, and Markesbery, WR, Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer’s disease and AD+DLB. J Alzheim Dis, 2008
Nelson PT*, Wang WX, Wilfred BR, Tang G. Technical variables in high-throughput miRNA expression profiling: Much work remains to be done. Biochim Biophys Acta. 2008 Apr 7.
Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, McManus MT. Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5614-9.
Wang WX, Wilfred BR, Baldwin DA, Isett RB, Ren N, Stromberg A, Nelson PT*. Focus on RNA isolation: Obtaining RNA for microRNA (miRNA) expression profiling analyses of neural tissue. Biochim Biophys Acta. 2008 Feb 13.
Wang, W-X, Nelson PT, and Tang, G, RNA interference and miRNA pathways: mechanisms and protein machinery. Wiley Encyclopedia of Chemical Biology. 2008
Wang W-X, Rajeev, BW, Stromberg AJ, Ren N, Tang G, Huang Q, Rigoutsos I, and Nelson PT*. The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of BACE1. J Neuroscience 2008 28(5): 1213-23.
Nelson PT*, Wang, W-X, and Rajeev, BW. MicroRNAs in neurodegeneration. Brain Pathology 2008 18(1): 130-8.
For a Powerpoint presentation by Dr. Nelson about exciting new ideas in RNA neurobiology, given for the Alzheimer Research Forum, click the following link. PowerPoint Presentation