RT Journal Article
SR Electronic
T1 Cerebral Amyloid Induces Aberrant Axonal Sprouting and Ectopic Terminal Formation in Amyloid Precursor Protein Transgenic Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8552
OP 8559
DO 10.1523/JNEUROSCI.19-19-08552.1999
VO 19
IS 19
A1 Amie L. Phinney
A1 Thomas Deller
A1 Martina Stalder
A1 Michael E. Calhoun
A1 Michael Frotscher
A1 Bernd Sommer
A1 Matthias Staufenbiel
A1 Mathias Jucker
YR 1999
UL http://www.jneurosci.org/content/19/19/8552.abstract
AB A characteristic feature of Alzheimer’s disease (AD) is the formation of amyloid plaques in the brain. Although this hallmark pathology has been well described, the biological effects of plaques are poorly understood. To study the effect of amyloid plaques on axons and neuronal connectivity, we have examined the axonal projections from the entorhinal cortex in aged amyloid precursor protein (APP) transgenic mice that exhibit cerebral amyloid deposition in plaques and vessels (APP23 mice). Here we report that entorhinal axons form dystrophic boutons around amyloid plaques in the entorhinal termination zone of the hippocampus. More importantly, entorhinal boutons were found associated with amyloid in ectopic locations within the hippocampus, the thalamus, white matter tracts, as well as surrounding vascular amyloid. Many of these ectopic entorhinal boutons were immunopositive for the growth-associated protein GAP-43 and showed light and electron microscopic characteristics of axonal terminals. Our findings suggest that (1) cerebral amyloid deposition has neurotropic effects and is the main cause of aberrant sprouting in AD brain; (2) the magnitude and significance of sprouting in AD have been underestimated; and (3) cerebral amyloid leads to the disruption of neuronal connectivity which, in turn, may significantly contribute to AD dementia.