Genetic analysis has identified 3 genes involved in early onset Alzheimer's disease, APP, and presenilin (PS) 1 and 2. Together mutations in these genes cause all autosomal dominant early onset disease. Apolipoprotein E(ApoE) is the only known risk factor for late onset disease although it does not explain all the familial clustering. Genetic analysis has led to the amyloid cascade hypothesis becoming the dominant theory underlying the etiology and pathogenesis of the disease, and this theory is being used to develop treatment strategies for the disease. A major project in our lab is to find the other genetic loci which contribute to disease and to determine how and whether variability at all loci affect amyloid metabolism. To this end, we are continually seeking to identify new mutations which lead to disease in the already-known genes, and also, in collaboration with investigators at Washington University and at Cardiff University (UK) we are carrying out genome screens in sibpairs to identify novel loci. Our work in this area has been the basis for our collaborators to make continually imporving cellular and animal models of AD. The work in these areas is also cited in this area

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000950-02
Application #
6815492
Study Section
(LNG)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sassi, Celeste; Nalls, Michael A; Ridge, Perry G et al. (2018) Mendelian adult-onset leukodystrophy genes in Alzheimer's disease: critical influence of CSF1R and NOTCH3. Neurobiol Aging 66:179.e17-179.e29
Chaudhury, Sultan; Patel, Tulsi; Barber, Imelda S et al. (2018) Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease. Neurobiol Aging 62:244.e1-244.e8
Patel, T; Brookes, K J; Turton, J et al. (2017) Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer's disease. Neuropathol Appl Neurobiol :
Mapstone, Mark; Lin, Feng; Nalls, Mike A et al. (2017) What success can teach us about failure: the plasma metabolome of older adults with superior memory and lessons for Alzheimer's disease. Neurobiol Aging 51:148-155
Sassi, Celeste; Ridge, Perry G; Nalls, Michael A et al. (2016) Influence of Coding Variability in APP-A? Metabolism Genes in Sporadic Alzheimer's Disease. PLoS One 11:e0150079
Sassi, Celeste; Nalls, Michael A; Ridge, Perry G et al. (2016) ABCA7 p.G215S as potential protective factor for Alzheimer's disease. Neurobiol Aging 46:235.e1-9
Escott-Price, Valentina; International Parkinson's Disease Genomics Consortium; Nalls, Mike A et al. (2015) Polygenic risk of Parkinson disease is correlated with disease age at onset. Ann Neurol 77:582-91
Peuralinna, Terhi; Myllykangas, Liisa; Oinas, Minna et al. (2015) Genome-wide association study of neocortical Lewy-related pathology. Ann Clin Transl Neurol 2:920-31
Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael et al. (2014) Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease. Neurobiol Aging 35:2881.e1-2881.e6
Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael et al. (2014) Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging 35:2422.e13-6

Showing the most recent 10 out of 98 publications