. Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci. 2008 Dec 31;28(53):14537-45. PubMed.

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  1. This is a very good study and I agree wholeheartedly with the results. It again shows that amyloid-β (Aβ) peptides do have a normal physiological role in the brain. Work from our group over the past few years has shown that Aβ42, in particular, is present in, and on, neurons in normal brains, and that the binding of exogenous Aβ42 to neuronal surfaces, including synapses, is mediated through the high affinity binding of Aβ42 to the α7 nicotinic acetylcholine receptor.

    This new work by Puzzo et al. again suggests a normal role for Aβ peptides in neurons, perhaps at the level of the synapse, that Aβ peptides are not toxic, and that the “purpose” of Aβ peptides and the enzymes that produce them, α- and γ-secretase, is not just to give us Alzheimer disease. Interestingly, it seems that the only difference between comparable neurons in normal and AD brains is that that latter seem to accumulate large quantities of Aβ sequestered in their lysosomal compartments, and many of these eventually die and undergo lysis to form a debris cloud referred to as classical, dense-core amyloid plaques. This study also emphasizes that exogenous Aβ has selective affinity for α7-rich regions of the brain parenchyma, and some of our more recent work has shown that the blood can serve as a chronic source of this Aβ in brain regions experiencing local breakdown of the blood-brain barrier.

    In short, I believe that these investigators are on the right track. Now the trick will be to get the rest of the field to take notice, stop “gnawing at the ends of old plots,” and finally allow fresh ideas to infiltrate the field that will lead to resolving this perplexing and devastating disease. Thank you for this refreshing electrophysiological study.