In vivo neurotoxicity of beta-amyloid [β(1–40)] and the β(25–35) fragment

doi:10.1016/0197-4580(92)90053-Z

Neurobiology of Aging

Volume 13, Issue 5, September–October 1992, Pages 537-542

https://doi.org/10.1016/0197-4580(92)90053-Z Get rights and content

Abstract

We examined the histological changes produced by injections of beta-amyloid [β(1–40)], and control peptides in rat and monkey cerebral cortex. β(25–35) injections were also studied in rat cortex. Standard immunoperoxidase procedures were used to detect the distribution of tau, MAP2, β(1–40) and ALZ 50 immunoreactivity. All injections produced localized necrosis at the injection site surrounded by a zone of neuronal loss and gliosis. In rat cortex, lesions produced by solubilized β(1–40) and β(25–35) in water were generally larger than those produced by control peptides. Tau and ALZ 50 antibodies labeled neurites and diffusely positive perikarya around β(1–40) injections, whereas MAP2 staining wasreduced, paralleling the distribution of neuronal loss and gliosis. In aged primate cortex, β(1–40) lesion size was dose dependent. Hyalinized, ALZ 50 positive neurons, and abnormal neurites were prominent around the injection site. Although β-amyloid is acutely neurotoxic in both rat and monkey cerebral cortex, neuronal degeneration in the primate more closely resembles that found in AD.

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Citation Excerpt :
Additionally, the potent toxic effect of fibrillar Aβ25–35 to neuronal cells and cultured hippocampal neurons has been demonstrated (Yankner et al., 1990; Kaneko et al., 1995), and Aβ25–35-induced neurotoxicity has been used in in vitro models to evaluate effects of causative agents of the neurodegeneration of AD (Calderon et al., 1999; Bothwell & Giniger, 2000). Furthermore, it has been proven that the Aβ25–35 fragments induce localized necrosis, neuronal and neuritic loss and the expression of AD antigens when injected in the contralateral hemisphere of the rat (Kowall et al., 1992; Emre et al., 1992). Moreover, the injection of Aβ25–35 into specific brain regions has been applied to induce AD-like pathological changes, such as impairments in long-term potentiation, activation of proapoptotic caspases, neuron loss in the hippocampus, and memory dysfunction, in animal models (Alkam et al., 2008; Meunier et al., 2006).
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In vivo neurotoxicity of beta-amyloid [β(1–40)] and the β(25–35) fragment

Abstract

Brain Res.

J. Neurol. Sci.

Lancet

Brain Res.

Neuroscience

Neuron

Chronic quinolinic acid lesions in rats closely resemble Huntington's disease

J. Neurosci.

Neurochemical characterization of excitotoxic lesions in the cerebral cortex

J. Neurosci.

A monoclonal antibody to neurofilament protein (SMI 32) labels a subpopulation of pyramidal neurons in the human and monkey neocortex

J. Comp. Neurol.

Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene

Nature

Degeneration of pyramidal projection neurons in Huntington's disease cortex

Ann. Neurol.