SMALL but catastrophic changes to genetic information as it passes between
gene and protein may be the most important cause of Alzheimer鈥檚 disease, say
Dutch scientists.
A group at the Netherlands Institute for Brain Research in Amsterdam has
found that small deletions in messenger RNA (mRNA), molecules that carry gene
codes to protein production sites in the cell, correlate with the build-up of
brain plaques in Alzheimer鈥檚 patients.
The brain plaques are made from an abnormal form of amyloid precursor protein
(APP). Earlier, the team found that small deletions in mRNA consisting of the
bases guanine (G) and adenine (A) resulted in the production of abnormal APP in
laboratory rats.
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To find out whether a similar process causes Alzheimer鈥檚 in humans, the team
looked at the brain tissue of people who had died with the disease. They say in
last week鈥檚 Science (vol 279, p 242) that they found the GA deletions in mRNA
coding for APP in every case. The abnormal mRNA was absent in controls who did
not have dementia.
Lead researcher Fred van Leeuwen says: 鈥淎s far as we鈥檙e aware it鈥檚 the first
time anyone has shown this. It could be a key factor in the development of
Alzheimer鈥檚 disease.鈥�
The researchers believe their results could explain the development of
Alzheimer鈥檚 in the majority of sufferers who have the non-hereditary form of the
disease. Faulty mRNA, unlike mutant genes, is not inheritable.
鈥淭hese findings are quite intriguing,鈥� says Gareth Roberts, an Alzheimer鈥檚
researcher at the Opine Consultancy in Cambridge. He believes they fit in with
the fact that head injuries and strokes make people more likely to develop the
disease. 鈥淲e know head trauma results in an increase in APP production,鈥� he
says. With this would come more of the abnormal APP. The discovery also raises
the possibility of new diagnostic tests for the disease. But, as yet, the
researchers have no idea what causes the damaging deletions in mRNA.