Mutation Linked to Particularly Aggressive form of Alzheimer's Disease

Researchers have identified a mutation linked to a late developing but particularly aggressive and untreatable form of Alzheimer's disease.

Approximately 20% of the population carries the mutated gene that encodes the K variant of butyrylcholinesterase (BChE-K). This enzyme degrades the neurotransmitter acetylcholine at a slower rate than does the enzyme produced by the normal gene. For this reason, affected individuals develop Alzheimer's disease later in life than do those carrying the normal gene.

What has puzzled researchers is the paradox that individuals with BChE-K develop a much more devastating form of the disease than their normal counterparts do. A recent paper in the June 19, 2009, issue of the Journal of Biological Chemistry presented findings that explain this anomaly.

Investigators at the Hebrew University of Jerusalem (Israel) compared the ability of mutated and normal BChE to prevent aggregation of beta-amyloid protein. They found that BChE-K, which differs from the native protein in the region of the C-terminus, was much less potent in its ability to prevent formation of beta-amyloid plaques. The accumulation of toxic amyloid plaques in brain cells characterizes advanced Alzheimer's disease.

The investigators suggested that treatment with a genetically engineered form of the normal BChE C-terminus region, which can be obtained from the milk of transgenic goats (prepared by PharmAthene Inc. (Annapolis, MD, USA), might provide protection from this form of Alzheimer's disease.

Related Links:
Hebrew University of Jerusalem
PharmAthene Inc.