There it is, the first publication from the NeuroD group in 2026. In this article, published in Neurobiology of Disease, Bas V., Ronald, and Willeke (in collaboration with Saskia Lesnik-Oberstein and Julie Rutten from Clinical Genetics, among others) describe a novel variant they found in the APP gene that leads to an APP p.V742L substitution in the APP intracellular domain.
What makes this variant so special is that it was found in a patient with ischemic strokes, something that has not previously been observed with pathogenic variants in APP (other pathogenic variants often lead to Alzheimer’s disease or cerebral amyloid angiopathy). In the article, the authors discuss the clinical presentation and describe the patient’s neuroradiological features.
They also demonstrate abnormal functioning of the APP p.V742L protein in the patient’s cells. They have discovered that APP p.V742L localizes differently in the cell and influences the regulation of gene expression. They also demonstrated that APP p.V742L binds more strongly to FE65, APP’s most important binding partner. Disrupting this crucial interaction could have significant consequences for APP function in the cell.
To read the whole paper, just click here
As always when someone publishes a paper, we had cake with one of the figures in the paper during our Monday morning meeting.
