A BIOCHEMICAL test which could turn out to be a promising 鈥渓ive鈥� marker for Alzheimer鈥檚 disease has been developed by scientists in Sweden and the US (Nature Medicine, vol 1, p 829). If successful, the test may also be used to monitor new drug treatments. At present Alzheimer鈥檚 disease can be diagnosed with certainty only after death, by looking for typical abnormalities in brain tissue.
Lars Lannfelt and his colleagues at the Karolinska Institute in Sweden have been trying to find something in the cerebrospinal fluid (CSF), which bathes the brain and spinal cord, that could help to identify people with Alzheimer鈥檚 disease while they are still alive. Samples of CSF can be taken from around the spinal cord via a lumbar puncture. Alzheimer鈥檚 disease is characterised by deposits in the brain, known as plaques, which are made up of a protein called beta-amyloid. So the researchers set out to see if they could detect any differences in the amount of beta-amyloid in the CSF of healthy people compared to patients with dementia.
Lannfelt says they were unable to find any differences in the levels of beta-amyloid in the CSF. But beta-amyloid is a small fragment of a larger molecule called amyloid precursor protein (APP). Another by-product of APP is a soluble product known as alpha-sAPP.
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When Lannfelt looked at the levels of Alpha-SAPP in CSF, he discovered that there was a very clear difference. 鈥淧eople with Alzheimer鈥檚 disease had low levels of this protein product in their CSF compared to healthy people,鈥� says Lannfelt.
But there are good reasons to be cautious about these findings. 鈥淭hese results came from testing just 14 members of one Swedish family, and we chose to do it that way because we already know that some people in this family carry a mutation on the APP gene which causes overproduction of amyloid and results in Alzheimer鈥檚 disease,鈥� says Lannfelt. 鈥淲e don鈥檛 know if we will find the same thing in people with dementia who have no known genetic tendencies to Alzheimer鈥檚 disease鈥�.
Kim Jobst and his colleagues at Oxford University believe they can help to answer some of these questions. They have been monitoring a large number of patients with dementia and healthy controls over the past seven years, and have collected samples of CSF from all of them. 鈥淚t would be interesting to test our CSF samples for alpha-sAPP to see if these differences are there in people who don鈥檛 come from the same family,鈥� says Jobst.