Extreme cerebrospinal fluid amyloid β levels identify family with late-onset Alzheimer's disease presenilin 1 mutation
Article first published online: 15 MAR 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 61, Issue 5, pages 446–453, May 2007
How to Cite
Kauwe, J. S. K., Jacquart, S., Chakraverty, S., Wang, J., Mayo, K., Fagan, A. M., Holtzman, D. M., Morris, J. C. and Goate, A. M. (2007), Extreme cerebrospinal fluid amyloid β levels identify family with late-onset Alzheimer's disease presenilin 1 mutation. Ann Neurol., 61: 446–453. doi: 10.1002/ana.21099
- Issue published online: 27 APR 2007
- Article first published online: 15 MAR 2007
- Manuscript Accepted: 18 JAN 2007
- Manuscript Revised: 17 JAN 2007
- Manuscript Received: 31 OCT 2006
- NIH (National Institute on Aging). Grant Numbers: P50-AG05681, P01-AG03991, P01-AG026276, R01-AG16208
- Washington University General Clinical Research Center (US Public Health System). Grant Number: M01-RR00036
- Ford Foundation Predoctoral Fellowship
Aggregation and deposition of amyloid beta (Aβ) in the brain is thought to be central to the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that cerebrospinal fluid (CSF) Aβ levels are strongly correlated with AD status and progression, and may be a meaningful endophenotype for AD. Mutations in presenilin 1 (PSEN1) are known to cause AD and change Aβ levels. In this study, we have investigated DNA sequence variation in the presenilin (PSEN1) gene using CSF Aβ levels as an endophenotype for AD.
We sequenced the exons and flanking intronic regions of PSEN1 in clinically characterized research subjects with extreme values of CSF Aβ levels.
This novel approach led directly to the identification of a disease-causing mutation in a family with late-onset AD.
This finding suggests that CSF Aβ may be a useful endophenotype for genetic studies of AD. Our results also suggest that PSEN1 mutations can cause AD with a large range in age of onset, spanning both early- and late-onset AD. Ann Neurol 2007;61:446–453