22 Oct 1998

Can transgenic mice serve as a truly useful model for studying Alzheimer's disease? Studies of mice expressing an APP gene mutation that causes a form of familial AD have reported no neuronal loss, despite the presence of amyloid plaques (see Irizarry journal club), raising such questions as whether amyloid kills neurons directly or whether mouse neurons are somehow invulnerable to amyloid toxicity. Now a study appearing in today's Nature, by Mathias Jucker and colleagues at the University of Basel, Switzerland, reports that mice with this gene mutation do apparently have reduced numbers of neurons in regions with heavy plaque burdens, particularly the CA1 pyramidal layer of the hippocampus. The reduction ranged from around 14 percent on average to 25 percent in animals with a high plaque load. Is this strong evidence that amyloid does kill neurons in mice? Perhaps, but even among normal mice, neuron counts can differ as much as 10 percent from one animal to another. The current study examined only 14 APP transgenics (including hetero- and homozygotes) and 10 controls, leading some observers to wonder whether the reduction reported is biologically meaningful.—June Kinoshita