Increased isoform-specific phosphodiesterase 4D expression is associated with pathology and cognitive impairment in Alzheimer’s disease

Pharmacological phosphodiesterase 4D (PDE4D) inhibition shows therapeutic potential to restore memory function in Alzheimer’s disease (AD), but will likely evoke adverse side effects. As PDE4D encodes multiple isoforms, targeting specific isoforms may improve treatment efficacy and safety. Here, we investigated whether isoform expression DNA methylation is affected AD changes are associated with severity of pathology cognitive impairment. In post-mortem temporal lobe brain material from patients (n = 42) age-matched controls 40), measured (hydroxy)methylation using quantitative polymerase chain reaction Illumina 450k Beadarrays, respectively. Linear regression revealed increased PDE4D1, -D3, -D5, -D8 concurrent promoter regions. Moreover, PDE4D1 -D3 was higherplaque tau levels, higher Braak stages, progressed Future studies should indicate functional roles the safety their selective AD.