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Posted by on Jun 24, 2008 in Neurology

Amyloid-Beta Dimers Induce Alzheimer’s-Like Findings in Rodents

Amyloid-Beta Dimers Induce Alzheimer’s-Like Findings in Rodents

Amyloid.jpg

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

  1. the inhibition of long-term potentiation (LTP) of synaptic transmission (a cellular model for learning and memory) in a dose-dependent fashion;
  2. enhanced long-term depression (LTD) (a marker of weakening synaptic transmission); and
  3. 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 autopsyas 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.

bmartin (1130 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.