ABSTRACT
Title
Predictive role of the scavenger receptor CD36 in course of neurodegeneration in APP23 mice
Authors
M. Giunta1, M. Morbin2, G. Giaccone2, S.M. Bonomo1, A.E. Rigamonti1, and S.G. Cella1
1Department of Medical Pharmacology, University of Milan, Italy
2Fondazione IRCCS Neurologic Institute Carlo Besta, Milan, Italy
1Department of Medical Pharmacology, University of Milan, Italy
2Fondazione IRCCS Neurologic Institute Carlo Besta, Milan, Italy
Abstract
Alzheimer’s disease (AD) represents about 70% of the dementing neurodegenerative pathologies. In the western countries its prevalence shows a trend toward a constant increase, so that it has become one of the main medical and social problems. AD is characterized by the amyloid-beta (Aβ) deposition in the brain, which represent the key element activating the microglial cells that, in turn, triggers oxidative and pro-inflammatory mechanisms. In fact, in an attempt to remove Aβ plaques, activated microglia express scavengers receptors, such as the multifunctional protein of class B type I CD36, which mediates the phagocytosis of Aβand induces the release of pro-inflammatory citokynes, reactive oxygen species and nitric oxide. Based on these observation it has been hypothesized that CD36 may play an important role in the pathogenesis of AD.
To test this hypothesis, we have studied the expression profile of CD36 in the course of neurodegeneration, using APP23 transgenic mice, a valid animal model which reproduces the main neuropathological changes associated to AD. Mice were evaluated at different ages (1,3,6,9 and 12 months), considering that neurodegeneration progressively worsens with the increasing age. We analyzed cortical and hippocampal mRNA and protein CD36 expression using, respectively, real-time PCR and immunostaining. Moreover, we also investigated the existence of a possible co-localization of CD36 and thioflavin-S, which stains for Aβplaques. Finally we analyzed CD36 gene expression in peripheral leukocytes since these cells, easy to obtain, share a common progenitor with microglia. Our aim was to investigate whether these elements may serve as a tool to investigate changes occurring in inaccessible brain areas.
The gene and protein expression of CD36 in the cortex and hippocampus of APP23 mice showed an incremental trend with a maximum at six months of age, returning then to lower values. Interestingly this changes occurred around the sixth months of age, i.e. in concomitance to the beginning of the Aβ plaque deposition in this animal model. Moreover, the co-staining with thioflavin-S showed an inverse relation between plaque and CD36 expression, implying for this receptor a protective role in the acute phase of the disease. Unlike that observed in the brain, CD36 gene expression in the leukocytes showed a progressive decremental trend starting from 6 months of age and reaching a minimum at 9 months of age and higher values in 12 months-old mice.
In conclusion, since currently a definitive diagnosis of AD is only possible through a post mortem exam, the characterization of a biological marker such as CD36 could be useful in the early diagnosis of AD, especially considering that its expression change from the early stages of the disease and is not related to the severity of neurodegeneration.
To test this hypothesis, we have studied the expression profile of CD36 in the course of neurodegeneration, using APP23 transgenic mice, a valid animal model which reproduces the main neuropathological changes associated to AD. Mice were evaluated at different ages (1,3,6,9 and 12 months), considering that neurodegeneration progressively worsens with the increasing age. We analyzed cortical and hippocampal mRNA and protein CD36 expression using, respectively, real-time PCR and immunostaining. Moreover, we also investigated the existence of a possible co-localization of CD36 and thioflavin-S, which stains for Aβplaques. Finally we analyzed CD36 gene expression in peripheral leukocytes since these cells, easy to obtain, share a common progenitor with microglia. Our aim was to investigate whether these elements may serve as a tool to investigate changes occurring in inaccessible brain areas.
The gene and protein expression of CD36 in the cortex and hippocampus of APP23 mice showed an incremental trend with a maximum at six months of age, returning then to lower values. Interestingly this changes occurred around the sixth months of age, i.e. in concomitance to the beginning of the Aβ plaque deposition in this animal model. Moreover, the co-staining with thioflavin-S showed an inverse relation between plaque and CD36 expression, implying for this receptor a protective role in the acute phase of the disease. Unlike that observed in the brain, CD36 gene expression in the leukocytes showed a progressive decremental trend starting from 6 months of age and reaching a minimum at 9 months of age and higher values in 12 months-old mice.
In conclusion, since currently a definitive diagnosis of AD is only possible through a post mortem exam, the characterization of a biological marker such as CD36 could be useful in the early diagnosis of AD, especially considering that its expression change from the early stages of the disease and is not related to the severity of neurodegeneration.