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

Abstract：

: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.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Delatour B,Blanchard V,Pradier L,Duyckaerts C

doi

10.1016/j.nbd.2004.01.008

keywords:

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

41-7

issue

1

eissn

0969-9961

issn

1095-953X

pii

S0969996104000130

journal_volume

16

pub_type

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