Two papers imply DTNB and other genes in Alzheimer’s

Two papers with LIGA contributions implicating rare variants in the DTNB and other genes in Alzheimer’s disease. The first paper (by Neumann et al.) utilized whole-exome sequencing data in a subset of participants of the EMIF-AD MBD study and utilized a novel analysis algorithm for CSF biomarker data to arrive at DTNB, FFO1, NLRC3 and SLC22A10 as putative disease genes. The study was led by our EMIF-AD collaborators at VIB in Antwerp and utilized CSF biomarker data which was combined by principal component analysis as outcome. The second study (by Prokopenko et al.) was led by our long-standing collaborators at Harvard Medical school and used whole-genome sequencing data in several family-based and case-control Alzheimer’s datasets. By applying a novel algorithm to group rare variants into genomic regions, this study, too, independently implicated rare variants in DTNB (and DLG2) to be linked to Alzheimer’s. DTNB (encoding: beta dystobrevin) is an interesting candidate owing to its role in postsynaptic membranes of excitatory synapses in the human brain. Both papers were published in the journal Molecular Psychiatry in Februrary and March of 2022.