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.

A SNP in the ACT gene associated with astrocytosis and rapid cognitive decline in AD.

Belbin O, Dunn JL, Chappell S, Ritchie AE, Ling Y, Morgan L, Pritchard A, Warden DR, Lendon CL, Lehmann DJ, Mann DM, Smith AD, Kalsheker N, Morgan K

Division of Clinical Chemistry, Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.

There is biochemical and animal model evidence supporting a pathological role of the ACT gene in AD. However, direct genetic evidence remains controversial and has been mostly limited to individual single nucleotide polymorphism (SNP) analysis. To resolve this apparent conflict we have used a high-density ACT SNP map, constructed haplotypes and explored correlations with phenotype. SNPs were identified by sequencing and used to construct haplotypes in 668 AD patients and 419 controls and a case-control association study was performed. Five SNPs, comprising five common haplotypes, represented 93% of ACT gene variation. Although no single SNP or haplotype was associated with AD status, a SNP in intron 2 was associated with later onset and more rapid cognitive decline (P=0.04). This SNP was both individually associated with severe astrocytosis (P=0.004) in AD patients and when combined with the signal sequence SNP (P=0.002). This suggests that astrocytosis may have a protective function for a limited period in some patients. These SNP associations either support a direct role for the ACT gene, in AD pathology or alternatively reflect linkage with polymorphisms in other genes nearby.

Published 23 June 2008 in Neurobiol Aging, 29(8): 1167-76.
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