title: Length-dependent gene misexpression is associated with Alzheimer's disease progression.
abstract: Recent reports show transcription preference for long genes in neuronal tissues compared with non-neuronal tissues, and a gene-length dependent change in expression in the neurodevelopmental disease Rett syndrome (RTT). Whether the gene-length dependent changes in expression seen in RTT might also be seen in neurodegenerative diseases is not yet known. However, a reasonable hypothesis is that similar effects might be seen in neurodegenerative diseases as well as in RTT since a common general feature of both illnesses involves progressive dysfunction of synapses. Here, we demonstrate a clear length-dependent gene misexpression in the most prevalent neurodegenerative disease, Alzheimer's disease. We show that the effect is associated with disease progression and can be attributed specifically to neurons. In particular, we observed gene length-dependent down regulation on the level of the whole tissue and gene length-dependent up regulation on the level of single cells. Our analysis shows that a gene-length effect on expression can be found in degenerative neurological illnesses, such as Alzheimer's disease. Additional investigation to elucidate the precise mechanism underlying gene-length dependent changes in expression is warranted.
authors.affiliation: Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, 1230 York Ave., New York, NY, 10065, USA. sbarbash@rockefeller.edu.
authors.forename: Shahar
authors.initials: S
authors.lastname: Barbash
authors.affiliation: Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, 1230 York Ave., New York, NY, 10065, USA. sakmar@rockefeller.edu.|Department of Neurobiology, Care Sciences and Society, Division for Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 141 57, Huddinge, Sweden. sakmar@rockefeller.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sakmar
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis