Brain loss isn't always disease culprit

Not all forms of dementia are the same, and researchers are starting to learn what distinguishes different forms of neurodegenerative dementias from each other. But one major problem remains -- most of the distinguishing pathological features of the diseases, such as protein accumulation and cell loss, can only be seen post mortem.

Prof Glenda Halliday, a researcher at the Prince of Wales Medical Research Institute at the University of NSW, outlined some of the differences between Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies at the Australian Neuroscience Society conference in Melbourne this week.

Unlike Alzheimer's disease and frontotemporal dementia, dementia with Lewy bodies does not involve significant cell loss, Halliday said. Instead, insoluble deposits of beta-amyloid -- the same protein implicated in Alzheimer's disease -- and alpha-synuclein are thought to cause dysfunction leading to the characteristic memory problems as well as fluctuating cognition and visual hallucinations seen in dementia with Lewy bodies patients.

"The lack of neurodegeneration in dementia with Lewy bodies makes this a potentially treatable disorder," Halliday said.

Like dementia with Lewy bodies, Alzheimer's disease is associated with the accumulation of extracellular beta-amyloid. Another deposited protein, tau, is also linked to the atrophy of cells in brains from Alzheimer's patients, and to frontotemporal dementia.

But in these two forms of dementia, the significant neuronal cell loss -- estimated to result in around two per cent of brain loss per year in Alzheimer's patients and up to 50 per cent total atrophy in the frontal and temporal lobes in frontotemporal dementia -- is thought to be due to an inflammatory glial cell response rather than to protein deposition.

"The association between tissue atrophy, pyramidal cell loss and inflammation points to the glia being important effectors for neurodegeneration," Halliday said.

By understanding the mechanisms that lead to the different forms of dementia, new ways of halting or even reversing neurodegeneration may be developed, according to Halliday. But more importantly, new imaging techniques are required to allow differentiation of the different forms of the disease in patients rather than post-mortem diagnosis, and that's where current research efforts are likely to pay off in the short term.

"People are working very hard to develop [more sensitive] imaging techniques that can diagnose dementias," she said.