biostudies-literaturePalomer EAlzheimers Research UKAlzheimer's Research UK (ARUK)Alzheimer's SocietyAlzheimer's Research UK3024-3033https://www.ebi.ac.uk/biostudies/studies/S-EPMC9205772biostudies-literatureUnknown27(7)Growing evidence supports a role for deficient Wnt signalling in Alzheimer's disease (AD). First, the Wnt antagonist DKK1 is elevated in AD brains and is required for amyloid-β-induced synapse loss. Second, LRP6 Wnt co-receptor is required for synapse integrity and three variants of this receptor are linked to late-onset AD. However, the expression/role of other Wnt signalling components remain poorly explored in AD. Wnt receptors Frizzled1 (Fzd1), Fzd5, Fzd7 and Fzd9 are of interest due to their role in synapse formation/plasticity. Our analyses showed reduced FZD1 and FZD7 mRNA levels in the hippocampus of human early AD stages and in the hAPP^NLGF/NLGF mouse model. This transcriptional downregulation was accompanied by reduced levels of the pro-transcriptional histone mark H4KMolecular psychiatryEpigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters.PMC9205772ARUK-2018DDI-UCLAS-PG-17-006ARUK-PG2018A-002Martin-Flores NWhiting PVaher KSaito TPalomer EPascual-Vargas PSalinas PCSaido TCJolly SPodpolny MTeo SBenvegnu SfalseEpigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters.Growing evidence supports a role for deficient Wnt signalling in Alzheimer's disease (AD). First, the Wnt antagonist DKK1 is elevated in AD brains and is required for amyloid-β-induced synapse loss. Second, LRP6 Wnt co-receptor is required for synapse integrity and three variants of this receptor are linked to late-onset AD. However, the expression/role of other Wnt signalling components remain poorly explored in AD. Wnt receptors Frizzled1 (Fzd1), Fzd5, Fzd7 and Fzd9 are of interest due to their role in synapse formation/plasticity. Our analyses showed reduced FZD1 and FZD7 mRNA levels in the hippocampus of human early AD stages and in the hAPP^NLGF/NLGF mouse model. This transcriptional downregulation was accompanied by reduced levels of the pro-transcriptional histone mark H4K2022-01-01T00:00:00Z2022 Jul2025-04-22T21:09:16.18Z2024-12-04T10:10:12.337ZS-EPMC92057723529680810.1038/s41380-022-01492-z