2018
DOI: 10.1007/s12035-018-1103-z
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Impaired Wnt Signaling in the Prefrontal Cortex of Alzheimer’s Disease

Abstract: Wnt pathway is involved in synaptic plasticity and neuronal survival, and alterations in Wnt signaling have previously been reported both in aging and neurodegenerative diseases, including Alzheimer's disease (AD). This study sought to evaluate Wnt signaling pathway interplay integrity across prefrontal lobe structures in AD patients compared to normal aging. Using the open-access BrainCloud™ database, 84 gene expression profiles and clustering effect were analyzed in the dorsomedial prefrontal cortex (PFC) ac… Show more

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Cited by 95 publications
(79 citation statements)
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“…We have interpreted these findings in light of the idea that SFRP1 acts as an endogenous inhibitor of ADAM10 in other contexts 12,13,22,25 . Our findings however are in apparent contradiction with the observation that in the brain SFRP1 expression increases with aging 69 and is upregulated in individual affected by Alzheimer's disease 13 , whereas it is barely detectable in the cortex of young and healthy individuals. We believe that this apparent discrepancy is linked to differential distribution of the protein in www.nature.com/scientificreports www.nature.com/scientificreports/ homeostatic conditions and the drastic alterations that occur during neurodegenerative events.…”
Section: Discussioncontrasting
confidence: 99%
“…We have interpreted these findings in light of the idea that SFRP1 acts as an endogenous inhibitor of ADAM10 in other contexts 12,13,22,25 . Our findings however are in apparent contradiction with the observation that in the brain SFRP1 expression increases with aging 69 and is upregulated in individual affected by Alzheimer's disease 13 , whereas it is barely detectable in the cortex of young and healthy individuals. We believe that this apparent discrepancy is linked to differential distribution of the protein in www.nature.com/scientificreports www.nature.com/scientificreports/ homeostatic conditions and the drastic alterations that occur during neurodegenerative events.…”
Section: Discussioncontrasting
confidence: 99%
“…Besides highlighting a specific role of Sfrp1 in the adult retina, our study provides an additional physiological example in which Sfrp1 likely acts as an endogenous inhibitor of ADAM10, a conclusion that matches our previous findings (12,13,21,23). In homeostatic conditions, Sfrp1 expression is barely detectable in the cortex of young and healthy individuals but it expression increases with aging (70) and is upregulated in individual affected by Alzheimer's disease (13). In this condition, activated glial cells (particularly astrocytes) produce SFRP1 leading to increased levels of toxic products of amyloid precursor protein processing (13) and further sustaining chronic inflammation (15).…”
Section: Discussionsupporting
confidence: 90%
“…Paraquat exposure altered the levels of the Wnt pathway genes in mouse neural progenitor cells [106], rotenone impaired Wnt signaling in a Drosophila PD model [107] and Deltamethrin also reduced Wnt signaling pathway genes in zebrafish's development of swim bladder [108]. Wnt signaling is known to be impaired in AD [109][110][111], and activation of the Wnt/β-catenin signaling pathway represses BACE-1 expression [112]. Activation of Wnt signaling has been shown to rescue memory loss and improves synaptic dysfunction in APP/PS1 AD transgenic mice [113,114].…”
Section: Enhancement Of Aβ and Tau Expression Modification And Clearmentioning
confidence: 99%