β-Amyloid of Alzheimer's Disease Induces Reactive Gliosis That Inhibits Axonal Outgrowth

doi:10.1006/exnr.1993.1199

Experimental Neurology

Volume 124, Issue 2, December 1993, Pages 289-298

https://doi.org/10.1006/exnr.1993.1199 Get rights and content

Abstract

Pathological lesions in the brains of patients with Alzheimer's disease (AD) are characterized by dense deposits of the protein β-amyloid. The link between the deposition of β-amyloid in senile plaques and AD-associated pathology is, at present, controversial since there have been conflicting reports on whether the 39-43 amino acid β-amyloid sequence is toxic or trophic to neurons. In this report, we show that β-amyloid peptide when presented as an insoluble substrate which mimics its conformation in vivo can induce cortical glial cells in vitro and in vivo to locally deposit chondroitin sulfate containing proteoglycan. In vitro the proteoglycan-containing matrix deposited by gila on β-amyloid blocks the usual ability of the peptide to allow cortical neurons to adhere and grow. Chondroitin sulfate-containing proteoglycan was also found in senile plaques of human AD tissue. We suggest that an additional effect of β-amyloid in the brain, which compounds the direct effects of βamyloid on neurons, is mediated by the stimulation of astroglia to become reactive. Once in the reactive state, glial cells deposit large amounts of growth-inhibitory molecules within the neuropil which could impair neuronal process survival and regeneration leading to neurite retraction and/or dystrophy around senile plaques in AD.

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Regular Articleβ-Amyloid of Alzheimer's Disease Induces Reactive Gliosis That Inhibits Axonal Outgrowth

Abstract

Regular Article
β-Amyloid of Alzheimer's Disease Induces Reactive Gliosis That Inhibits Axonal Outgrowth