DATA MAY LEAD TO ALZHEIMER'S TESTClinical researchers have found two important clues to themolecular basis of Alzheimer's disease, according to paperspublished in Friday's issues of The Lancet and Nature. Theseclues may lead to improved diagnostic tools and therapeutics.

One of the signs of Alzheimer's disease is a loss of activity inone of the major brain neurotransmitter systems, thecholinergic system. A team at Oxford University in Englandfound an abnormal form of a key cholinergic enzyme in thecerebrospinal fluid (CSF) of Alzheimer's patients.

Dr. D.S. Navaratnam and colleagues reported in The Lancet on astudy involving 33 patients with clinically diagnosed dementia(one of the symptoms of Alzheimer's and otherneurodegenerative diseases), nine with possible dementia and19 with no clinical signs of dementia. The team analyzed theCSF of the patients for the presence of abnormal forms ofacetylcholinesterase (AChE), an enzyme in the cholinergicsystem that is found in many of the regions of the brainaffected by Alzheimer's. The researchers found evidence of anabnormal form of AChE in 21 of the 33 dementia patients andfour of the nine patients with suspected dementia. Thisabnormal AChE was not found in any of the samples from the19 non-dementia patients.

If the correlation between the abnormal AChE and Alzheimer'sholds up, this may become the basis for a much-neededdiagnostic test for Alzheimer's in living patients. Such a testwould be a boon for the numerous biotech and pharmaceuticalcompanies that are developing therapeutic agents for thismajor health care problem. Currently, these companies cannotobjectively follow the effectiveness of any therapeutic agentsuntil the patients die.

The Nature report, by The Alzheimer's Disease Research Groupat St. Mary's Hospital Medical School in London, andcollaborators at Yale University and the University of WalesCollege of Medicine, found an association between Alzheimer'sand a mutation in the amyloid precursor gene.

The researchers used polymerase chain reaction (PCR)technology to amplify the target gene sequence containing themutation. They identified the presence of a single amino acidmutation within the transmembrane domain of the amyloidprecursor protein in a family whose members suffer fromearly-onset Alzheimer's. The amyloid precursor protein isthought to contain the message encoding the source of theamyloid plaque that is found in the brains of Alzheimer'spatients.

The team found no evidence of the mutation in 100 unrelated,healthy individuals and 14 patients with late-onset disease.However, screening of 18 patients with early-onset Alzheimer'sshowed that the mutation occurred in a second family.

The researchers suggest that this mutation is probably one ofthe genetic manifestations of Alzheimer's, acting to generate anabnormal amyloid protein that is deposited into plaques.

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