Amyloid-Beta Dimers Induce Alzheimer’s-Like Findings in Rodents
For the first time, researchers showed that amyloid beta (Aβ) dimers from the brains of individuals with Alzheimer’s disease induce several AD-like changes in normal rodents. The results of a series of related experiments were reported in the latest online edition of Nature Medicine.
AD-consistent pathophysiologic changes were observed in the normal rodent hippocampus after it was exposed to soluble (but not insoluble) Aβ. The investigators, from Boston and Ireland, discovered
- the inhibition of long-term potentiation (LTP) of synaptic transmission (a cellular model for learning and memory) in a dose-dependent fashion;
- enhanced long-term depression (LTD) (a marker of weakening synaptic transmission); and
- reduced dendritic spine density (a marker of synaptic loss).*
The administration of the Aβ dimer also disrupted the learning of a standard avoidance task in rats. Antibodies to the N-terminus of Aβ prevented the dimer’s effects on LTP and LTD (which requires metabotropic glutamate receptors); however, the effect of antibodies to other regions of Aβ was not as remarkable.
The fact that AD-like changes were not detected with insoluble Aβ or other oligomers of Aβ may explain the disconnect between relatively preserved cognitive function during life and a high burden of Aβ in some brains at autopsy—as Marcelle Morrison-Bogorad, director of the neuroscience division at the National Insititute on Aging (NIA), told the AP. The Nature Medicine study was funded, in part, by the NIA.
* The authors note that decreased synaptic density is the strongest neuropathologic correlate of dementia in AD.
Image of wild-type amyloid precursor protein (left) and amyloid fibril (right) by David S. Goodsell from Wikimedia Commons.