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Publication : Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model.

First Author  Delatour B Year  2004
Journal  Neurobiol Dis Volume  16
Issue  1 Pages  41-7
PubMed ID  15207260 Mgi Jnum  J:91228
Mgi Id  MGI:3046144 Doi  10.1016/j.nbd.2004.01.008
Citation  Delatour B, et al. (2004) Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model. Neurobiol Dis 16(1):41-7
abstractText  It has been proposed that Alzheimer disease (AD) is associated with a 'disconnection syndrome' due to the gradual loss of morphological and functional integrity of cortico-cortical pathways. This hypothesis derives from indirect neuropathological observations, but definitive evidence that AD primarily targets cortico-cortical networks is still lacking. By means of neuroanatomical anterograde tracing methods, we have investigated, in a murine transgenic model of AD, the impact of the amyloid burden on axonal terminals in different neural systems. Axonal tracings revealed, in accordance with the 'disconnection syndrome' hypothesis, that cortico-cortical fibers are significantly disorganized. Terminal fields in local and distant cortical areas contained numerous swollen dystrophic neurites often grouped in grape-like clusters at the plaque periphery. In contrary to fibers of cortical origin, those originating from subcortical brain structures only showed limited signs of degeneration upon reaching their cortical targets. These observations suggest a selective disruption of cortico-cortical connections induced by AD brain pathology.
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