05 Oct 2004

Memory is such an intrinsic part of who we are that when it is lost, so are we. Yet, despite terrific biological advances over the last few decades, we have only a rudimentary understanding of the processes involved in learning, storing, and recollecting information. So what do we know? A special section in the September 30 Neuron reviews some of the advances that have been made in recent years and explores some areas that may prove extremely fruitful in the near future.

Of particular interest to those studying Alzheimer disease are reviews from Randy Buckner at Washington University, St. Louis, and Dominic Walsh and Dennis Selkoe at University College Dublin and Harvard Medical School, respectively.

Buckner contends that factors that lead to aging are not the same as those that lead to AD. In normal aging, loss of executive function, which can be distinguished from AD-related memory losses, is more common. “In advanced aging,” he writes, “frontal-striatal systems are preferentially vulnerable to white matter change, atrophy, and certain forms of neurotransmitter depletion.” In AD, however, the medial temporal lobe and cortical networks are primarily targeted, Buckner notes. He also reviews recent literature which suggests that reserve compensatory factors can influence how rapidly a person ages mentally. Cognitive reserve, he contends, can explain why, of two people with similar brain decline, one will be devastated while the other is seemingly unaffected.

Walsh and Selkoe assess the molecular basis for AD. Their review centers on the role played by amyloid-β (Aβ) peptides, particularly focusing on the recent evidence that has uncovered the toxic nature of Aβ. “Diverse lines of evidence now suggest that Aβ plays a central role in the pathogenesis of neuronal dysfunction in AD,” they write. Yet the Aβ cascade hypothesis remains controversial because there is no direct relationship between the number of amyloid plaques and the severity of the disease. Addressing this issue, the authors review findings that demonstrate soluble Aβ can perturb synaptic function, block long-term potentiation, and disrupt synaptic plasticity, memory, and learned behavior.

Other reviews include one on long-term potentiation and long-term depression by Robert Malenka and Mark Bear, a discussion of the role of translation in memory by Susumu Tonegawa and colleagues, and the role of the neocortex in memory consolidation by Alcino Silva and colleagues. The full citation list is included below.—Tom Fagan