Early-Stage lnflammation and Experimental Therapy in Transgenic Models of the Alzheimer-Like Amyloid Pathology

A.C. CUELLO M.T. FERRETTI W.C. LEON M.A. BRUNO F. CANNEVA

NEURODEGENERATIVE DISEASES

KARGER

Año: 2010 p. 96 - 98

1660-2854

Intracellular accumulation of B-amyloid (AF) isaccumulation of B-amyloid (AF) is one of the early features in the neuropathology of Alzheimer´s disease (AD) and Down´s syndrome. This can be reproduced disease (AD) and Down´s syndrome. This can be reproduced of the early features in the neuropathology of Alzheimer´s disease (AD) and Down´s syndrome. This can be reproduced(AD) and Down´s syndrome. This can be reproduced in cell and transgenic animal models of the AD-likecell and transgenic animal models of the AD-like amyloid pathology. In a transgenic rat model, our lab haspathology. In a transgenic rat model, our lab has previously shown that the intracellular accumulation of ABthat the intracellular accumulation of AB is sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus in alterations in the cerebral cortex and hippocampus in sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus inin the cerebral cortex and hippocampus in the absence of amyloid plaques. Objective:To investigate anabsence of amyloid plaques. Objective:To investigate an ea rl y, pre-plaq ue inf la m matory process in AD-like tra nsgenicrl y, pre-plaq ue inf la m matory process in AD-like tra nsgenic models and establish whether the neurotoxic effects of ABwhether the neurotoxic effects of AB oligomers and proinflammatory responses can be arrestedresponses can be arrested with minocycline. Methods: For these studies, we used nalve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical pathology and applied neurochemical, immunohistochemical mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical pathology and applied neurochemical, immunohistochemical minocycline. Methods: For these studies, we used nalve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical pathology and applied neurochemical, immunohistochemical and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemicaland applied neurochemical, immunohistochemical and behavioral experimental approaches. Results.´ In theexperimental approaches. Results.´ In the early stages of the AD-like amyloid pathology,intracellular AB oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD. cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD. AB oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD. cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD. of the AD-like amyloid pathology,intracellular AB oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD. cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD. oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioraland hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloidoccur prior to the appearance of amyloid plaques, together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatment COX-2, well-known proinflammatory markers. Treatment together with an upregulation of MHC-ll, i-NOS and COX-2, well-known proinflammatory markers. Treatmentwell-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, loweredminocycline corrected behavioral impairments, lowered inflammatory markers and levels of AB trimers. Conclusion:markers and levels of AB trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatorytargeting the early neuroinflammatory effects of AB might be a promising strategyAB might be a promising strategy to prevent or delay the onset of AD.prevent or delay the onset of AD.