Several late-breaking, dramatic results were presented at this final symposium of the meeting. Michael Hutton and colleagues from Mayo Laboratory, Jacksonville, which only a few days earlier had first publicly presented data showing tangles and neurodegeneration in an FTDP-17 tau (P301L) transgenic mouse, revealed that double transgenics expressing the Swedish APP mutation and P301L tau also had NFTs and neuropathology, as well as Aβ plaques.

Yong Shen of Sun Health Research Institute described a successful method to culture neurons harvested postmortem from sporadic AD brain. He noted that the AD neurons developed fewer processes but, curiously, lived longer than neurons cultured from normal adult brains. It will be of great interest to examine the molecular and cell biology of the AD neuronal cultures, and they offer an intriguing possibility for drug assays.

David Morgan from University of South Florida presented data showing that Aβ vaccination blocked cognitive deficits in PS/APP double transgenic mice. Using a novel spatial learning task-a six-arm radial water maze-the USF investigators found that 12-month-old and 15-month-old mice that had received a course of vaccinations from four months of age onward performed as well as control animals, learning to navigate the maze with few errors. In contrast, age-matched nonimmunized mice were unable to learn the task and performed at chance. What’s more, 15-month-old mice that received a shorter course of vaccinations also improved to almost the same performance level as the controls. Fascinatingly, the 15-month-olds that had short-term vaccination had almost no reduction in Aβ burden compared to nonimmunized mice, suggesting that the plaques per se were not responsible for the observed cognitive deficits. One possible explanation is that immunization is leading to clearance of solube Aβ, which is causing the impaired function.

One hypothesis to emerge from the Aβ vaccination studies is that plaques may accumulate in Alzheimer’s patients because they are unable to clear Aβ as effectively as people who don’t get Alzheimer’s. Yangsheng Du presented data to support this notion, showing that CSF from Alzheimer's patients had a 30% reduction in levels of Aβ antibodies.

Miguel Pappolla presented data showing that high doses of melatonin produced dramatic drops in Aβ in the Tg2576 ("Hsiao") mouse. The mice were given around 1.5 mg per day of melatonin from age four months onward, and sacrificed at 15 months. The melatonin also produced "significant improvement" in performance on the Morris water maze, Pappolla reported.

In the final talk, Barry Reisberg presented preliminary results from the first U.S. clinical trial of memantine, a drug that targets the NMDA receptor system and which has been marketed in Germany. In the study, 126 patients with moderately severe to severe Alzheimer’s received 10 mg doses of memantine twice a day, while 126 matched controls received placebo. After six months, the treated patients were found to decline more slowly than the placebo group on a number of standard measures (which I was unable to note down because the data flashed by so quickly). Thus memantine may hold promise as a treatment for more advanced Alzheimer’s, for which there are currently no therapies.—June Kinoshita


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