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.

Allele-specific overexpression in astrocytes of an Alzheimer's disease associated alpha-1-antichymotrypsin promoter polymorphism.

Ritchie A, Morgan K, Kalsheker N

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

Alpha-1-antichymotrypsin (ACT), a serine proteinase inhibitor is synthesised predominantly in the liver and in other tissues including the brain. ACT is a major component of the senile plaques (SP) characteristic of Alzheimer's disease (AD). Increased production locally in the brain may be associated with Alzheimer's disease as ACT acts as a "pathological chaperone", promoting beta-amyloid assembly into neurotoxic fibrils. Recent reports suggest that the T allele of a G/T polymorphism at position -51 of ACT is associated with cognitive decline in AD patients. We demonstrate that the T allele is markedly overexpressed by almost 225% in an astrocytic cell line in response to oncostatin M (OSM) compared with a 35% increase in a mixed population of brain-derived cells. This effect is probably mediated by a higher binding affinity of the transcription initiation complex to the higher expressing allele and overexpression of ACT by astrocytes could thus contribute to increased beta-amyloid fibril formation in AD.

Published 8 November 2004 in Brain Res Mol Brain Res, 131(1): 88-92.
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