Australasian Science: Australia's authority on science since 1938

Brain Plaques Don’t Indicate Alzheimer’s Onset

By Stephen Luntz

The debate about the causes of Alzheimer’s disease has turned again, with the publication in PLoS ONE of evidence that plaque only appears after memory loss has begun.

The finding suggests that plaque is not a useful test for the early stages of Alzheimer’s, and could have a substantial influence on the search for cures.

“Ever since Alois Alzheimer first described this disease in 1906, plaque has been regarded as the definitive Alzheimer’s diagnosis,” said project leader Dr Bryce Vissel of the Garvan Institute of Medical Research. Since plaque could not be detected until after death, the timing of its appearance was hard to determine but was thought to precede, or at least coincide with, early dementia symptoms.

However, plaque detection is now possible using positron emission tomography (PET) in living people. This was thought to offer potential for early Alzheimer’s diagnosis but Vissel says: “Our study suggests that this method may not be accurate in earlier disease stages”.

Instead, Vissel found that nerve cell loss and inflammation appear earlier. His work was done with a mouse model, requiring painstaking counting of the number of nerve cells and measurement of inflammation at five different ages of mice with a gene for Alzheimer’s disease. Two other groups released similar conclusions from different methodologies this year.

With billions of dollars of research funding chasing a method of preventing or slowing the development of plaques, so far with little result, some researchers are suggesting that the Tau protein would be a better target (AS, March 2012, p.6). Vissel says inflammation also needs to be considered, but it is not as simple as one being the cause and the others symptoms.

“There is a lot of work suggesting Alzheimer’s is a disease of the immune system. However, there are a lot of very intelligent people who think plaques are the issue, and some research shows that if you can remove the plaques in mouse models you get some rescue,” Vissel says.

“We need to come up with a unified idea,” Vissel argues. “It could be that Alzheimer’s is falsely regarded as a single disease and is actually several diseases – in some cases plaque as the driver, in some cases tau and in some cases inflammation. The other possibility is they are all part of a similar mechanism.

“We lean towards the latter: that plaque and tau and inflammation are all part of a cycle. Depending on the initiation event some may be more prominent than others.”

High hopes for trials of drugs to treat Alzheimer’s have been met with disappointment in recent years. “It would be consistent with our work that drugs need to be started earlier,” Vissel says. However, this requires better diagnosis, for which it was thought PET might provide the answer.

Vissel also thinks the drugs might work on a subset of Alzheimer’s patients, in which the amyloid-beta that forms the plaques is over-expressed.

Vissel doubts that classic anti-inflammatory drugs will work if inflammation is the trigger for the problem. “You’ll need something more specific, but we are looking at ways to do that.”