Abstract
Leucine-rich repeat kinase 2 (LRRK2) mutation carriers can develop clinical symptoms other than typical parkinsonism such as dementia, amyotrophy or dystonia. To determine if LRRK2 mutations might be involved in frontotemporal dementia (FTD), 5 individuals with multiplex familial FTD kindreds and 41 pathologically confirmed cases of FTD, including 23 with a family history of dementia, were screened for genetic variations in the LRRK2 gene. We identified a LRRK2 mutation leading to the G2019S amino acid substitution in a 79-year-old woman with frontotemporal lobar degeneration with ubiquitinated neuronal intranuclear inclusions (FTLD-U/NII) and a possible family history of tremor. These findings may be coincidental; however, there is a small nucleus of LRRK2-positive patients displaying atypical features suggesting a role for this protein in other neurodegenerative disorders.
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Acknowledgments
We are grateful to the following organizations for their support of this work: The Morris K. Udall Center for Excellence in Parkinson’s disease research at Mayo Clinic (P50 NS40256), the Mayo Clinic Alzheimer Disease Research Center (P50 AG16574), P01 AG17216 and the brain banks of the State of Florida Alzheimer Disease Initiative and the Society for Progressive Supranuclear Palsy. OAR is a recipient of a Robert H. and Clarice Smith Fellowship. We thank Minnie Schreiber for technical assistance. We would also like to thank the donors and their families.
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Dächsel, J.C., Ross, O.A., Mata, I.F. et al. Lrrk2 G2019S substitution in frontotemporal lobar degeneration with ubiquitin-immunoreactive neuronal inclusions. Acta Neuropathol 113, 601–606 (2007). https://doi.org/10.1007/s00401-006-0178-1
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DOI: https://doi.org/10.1007/s00401-006-0178-1