Jill R. Murrell, PhD
Departments of Pathology and Laboratory Medicine and Medical and Molecular Genetics
Indiana University School of Medicine
Laboratory telephone: 317-274-2819
My training and research interests focus on neurogenetics specifically the genetics of dementia, Alzheimer Disease (AD) and Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Over the past fifteen years, my laboratory has processed, genotyped, distributed and/or stored over 5000 human samples from various studies examining dementia and cognitive function. One such study is the Indiana Alzheimer Disease Center (IADC), which is funded by the National Institutes of Aging. The IADC has excelled in the collection and investigation of familial dementia. My laboratory provides molecular genetic diagnosis, performs genotyping of risk factors such as apolipoprotein E (APOE), candidate gene sequencing and supplies genetic material to national/international researchers and the Alzheimer’s Disease Genetic Consortium. The repertoire of the laboratory has evolved recently especially in the area of FTD-ALS in which several different genes have been identified to cause this devastating disease.
Research is also being conducted to determine risk factors for dementia and/or cognitive decline in individuals of African ancestry. For the past twenty years, two unique elderly cohorts, one from Indianapolis and the other from Ibadan Nigeria have been studied and the data collected has added greatly to the understanding of cognition in these understudied ethnic groups. Specifically, we have found that APOE4 is a risk factor for African Americans but not Africans. This difference may be due to unique environmental stresses resulting in variable gene expression within the two populations. Global epigenetic studies are being planned to test this hypothesis. Currently, genome wide association studies are being completed using the DNA from approximately 3,000 subjects. The goal is to identify genetic factors associated with cognitive decline in African Americans and the Yoruba.
Another phase of the research is the study of mutations in the MAPT gene that cause frontotemporal dementia and parkinsonism. MAPT encodes the tau protein, which is involved in several sporadic and familial dementias such as AD, progressive supranuclear palsy and Pick disease. Tau is a microtubule-associated protein that functions in the assembly and stabilization of microtubules. Analyses of familial forms of frontotemporal dementia have led to the discovery of numerous mutations in MAPT. Since the discovery of MAPT mutations in families with these diseases, the major focus of our research has been in studying how these mutations result in disease. A transgenic mouse model expressing a human mutated MAPT transgene has been produced. This model exhibits tau deposition in the central nervous system and has a phenotype that affects the motor system. These animals can be used to test potential therapies directed to tau pathology. Future studies include detailed brain imaging analyses. Currently, the animals are being bred with other transgenic models to achieve more precise models for other human neurodegenerative diseases.
Murrell J, Farlow M, Ghetti B, et al. 1991. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's Disease. Science 254:97-99.
Murrell J, Spillantini MG, Zolo P, et al. 1999. Tau gene mutation G389R causes a tauopathy with abundant Pick body-like inclusions and axonal deposits. 58(12):1207-1226.Murrell J, Hake A, Quaid KA, et al. 2000. Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein. Arch Neurol 57(6):885-887.
Gureje O, Ogunniyi A, Baiyewu O, Price BM, Unverzagt F, Evans, R, Smith-Gamble V, Lane KA, Gao S, Hall K, Hendrie H, Murrell J. 2006. APOE4 is not associated with Alzheimer's Disease in elderly Nigerians. Annals of Neurology. 59:182-185.
Hall K, Murrell J, Ogunniyi A, Deeg M, Baiyewu O, Gao S, Gureje O, Dickens J, Evans R, Smith-Gamble V, Unverzagt FW, Shen J, Hendrie H. 2006. Cholesterol, APOE genotype and Alzheimer's disease: An epidemiological study of Nigerian Yoruba. Neurology. 66(2):223-227.
Murrell J, Price BM, Lane KA, Baiyewu O, Gureje O, Ogunniyi A, Unverzagt FW, Smith-Gamble V, Gao S, Hendrie HC, Hall K. 2006. Apolipoprotein E Genotype Associated with Alzheimer's Disease in African Americans. Archives of Neurology. 63(3):431-434.Murrell J, Price BM, Baiyewu O, Gureje O, Deeg M, Hendrie H, Ogunniyi A, Hall K. 2006. The Fourth Apolipoprotein E Allele Found in the Yoruba of Ibadan. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 141B(4):426-7.
Murrell J, Ghetti B, Cochran E, Macias-Islas MA, Medina L, Varpetian A, Cummings JL, Mendez MF, Kawas C, Chui H, Ringman JM. 2006. The A431E Mutation in PSEN1 causing Familial Alzheimer's Disease Originating in Jalisco State, Mexico: An Additional Fifteen Families. Neurogenetics. 7(4):277-279.Spina S, Murrell JR*, Huey ED, Wassermann E, Pietrini P, Baraibar MA, Barbeito AG, Troncoso JC, Vidal R, Ghetti B, Grafman J. 2007. Clinicopathological features of frontotemporal dementia with Progranulin sequence variation. Neurology. 68(11):820-7. * co-first author.
Spina S, Farlow MR, Unverzagt FW, Kareken DA, Murrell JR, Fraser G, Epperson F, Crowther RA, Spillantini MG, Goedert M, Ghetti B. 2008. The tauopathy associated with mutation +3 in intron 10 of Tau: Longitudinal characterization of the MSTD kindred. Brain. 131:72-89.
Gao S, Jin Y, Hall K, Liang C, Unverzagt F, Ma F, Cheng Y, Shen J, Cao J, Matesan J, Li P, Bian J, Hendrie H, and Murrell J. 2009. Selenium Level is Associated with Apolipoprotein E4 in Rural Elderly Chinese. Public Health Nutr. 12:2371-2376.
Kovacs GG, Murrell JR, Horvath S, Haraszti L, Majtenyi K, Molnar MJ, Budka H, Ghetti B, Spina S. 2009. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy and chorea. Movement Disorders. 24(12):1843-7.
Campbell NL, Boustani MA, Lane KA, Gao S, Hendrie H, Khan BA, Murrell JR, Unverzagt FW, Hake A, Smith-Gamble V, Hall K. 2010. Use of Anticholinergics and the Risk of Cognitive Impairment in an African-American Population. Neurol. 75(2):152-9.
Hagen MC, Murrell JR, Delisle MB, Andermann E, Andermann F, Guiot MC, Ghetti B. 2011. Encephalopathy with Neuroserpin Inclusion Bodies Presenting as Progressive Myoclonus Epilepsy and Associated with a Novel Mutation in the Proteinase Inhibitor 12 Gene. Brain Pathol. 21(5):575-82.
Ogunniyi A, Lane KA, Baiyewu O, Gao S, Gureje O, Unverzagt FW, Murrell JR, Smith-Gamble V, Hall KS, Hendrie HC. 2011. Hypertension and incident dementia in community-dwelling elderly Yoruba Nigerians. Acta Neurol Scand. 124(6):396-402.