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

Autor: B Delatour, V Blanchard, L Pradier, C Duyckaerts
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Zdroj: Neurobiology of Disease, Vol 16, Iss 1, Pp 41-47 (2004)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2004.01.008
Popis: 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.
Databáze: Directory of Open Access Journals