Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation.

Kauwe JS, Jacquart S, Chakraverty S, Wang J, Mayo K, Fagan AM, Holtzman DM, Morris JC, Goate AM

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

OBJECTIVE: Aggregation and deposition of amyloid beta (Abeta) in the brain is thought to be central to the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that cerebrospinal fluid (CSF) Abeta 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 Abeta levels. In this study, we have investigated DNA sequence variation in the presenilin (PSEN1) gene using CSF Abeta levels as an endophenotype for AD. METHODS: We sequenced the exons and flanking intronic regions of PSEN1 in clinically characterized research subjects with extreme values of CSF Abeta levels. RESULTS: This novel approach led directly to the identification of a disease-causing mutation in a family with late-onset AD. INTERPRETATION: This finding suggests that CSF Abeta 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.

Published 3 May 2007 in Ann Neurol, 61(5): 446-53.
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