The non-Alzheimer dementias include Pick's disease, Frontal Temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal degeneration, Parkinson's dementia complex of Guam and dementia without specific histological features. Our group has been working on these rare disease (which together, probably affect about 1/4 of the number of AD sufferers: that is ~500,000 Americans). Our intention is to elucidate the mechanisms of these diseases through genetic analysis so that we can model them in cells and animals as we and others have successfully done in Alzheimer's disease. In addition, since many of these diseases share pathological features, especially tangles, with Alzheimer's disease, these genetic analyses and the models we make using the genetic information, is of value in elucidating the pathgenic mechanisms in Alzheimer's disease. Our group was part of the consortium which showed that mutations in the tau gene caused Pick's disease/FTDP-17 and that showed that tau was a predisposing locus for PSP and CBD and we continue to look for new tau mutations and for families with frontal dementia in which tau is not the pathogenic locus. Of particular note: this year we have completely defined the extent of the tau haplotype, limiting the region in which we know that genetic variability which predisposes to PSP and CBD occurs .

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000951-03
Application #
6969684
Study Section
(LNG)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Guerreiro, Rita; Ross, Owen A; Kun-Rodrigues, Celia et al. (2018) Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol 17:64-74
Kun-Rodrigues, Celia; Ross, Owen A; Orme, Tatiana et al. (2017) Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies. Neurobiol Aging 49:214.e13-214.e15
Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee et al. (2016) Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases. Neurobiol Aging 38:214.e7-214.e10
Sassi, Celeste; Capozzo, Rosa; Gibbs, Raphael et al. (2016) A Novel Splice-Acceptor Site Mutation in GRN (c.709-2 A>T) Causes Frontotemporal Dementia Spectrum in a Large Family from Southern Italy. J Alzheimers Dis 53:475-85
Tranah, Gregory J; Yokoyama, Jennifer S; Katzman, Shana M et al. (2014) Mitochondrial DNA sequence associations with dementia and amyloid-? in elderly African Americans. Neurobiol Aging 35:442.e1-8
Federoff, Monica; Jimenez-Rolando, Belen; Nalls, Michael A et al. (2012) A large study reveals no association between APOE and Parkinson's disease. Neurobiol Dis 46:389-92
Tranah, Gregory J; Nalls, Michael A; Katzman, Shana M et al. (2012) Mitochondrial DNA sequence variation associated with dementia and cognitive function in the elderly. J Alzheimers Dis 32:357-72
Pearson, Justin P; Williams, Nigel M; Majounie, Elisa et al. (2011) Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p. J Neurol 258:647-55
Guerreiro, Rita Joao; Baquero, Miquel; Blesa, Rafael et al. (2010) Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging 31:725-31
Guerreiro, Rita J; Washecka, Nicole; Hardy, John et al. (2010) A thorough assessment of benign genetic variability in GRN and MAPT. Hum Mutat 31:E1126-40

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