In this week's PNAS, research led by Stanford University scientists studied antibodies to β-amyloid (Aβ) proteins on a large scale. Using peptide arrays on plasma samples and cerebrospinal fluid of patients with Alzheimer's disease, they found natural antibodies against known toxic Aβ and amyloidogenic non-Aβ peptides and that these antibodies decrease with age and advancing Alzheimer's. Antibody reactivity was "most prominent against oligomeric assemblies of Aβ and pyroglutamate or oxidized residues," suggesting there are "conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides," they write.
Scientists at the Gladstone Institute in San Francisco have published a paper on the pathways involved in frontotemporal dementia, which is the most common form of dementia in people under 60. In work led by first author S. Tariq Ahmad, they used a genetic screen on a Drosophila model of frontotemporal dementia to find that serpin5, a serine protease inhibitor, regulates the toll pathway and CHMP2B toxicity. Rare mutations in the CHMP2B gene have been found to be associated with frontotemporal dementia.
At the Genome Institute of Singapore, Sen-Kwan Tay led work published this week that looked at the "genomic basis of primate phenotypic uniqueness." After screening a catalog of 38,037 human transcriptional units (TUs), the team discovered 131 of these within primate-specific insertions in nine-species sequence alignments and outside of segmental duplications. Among other things, they found that 24 percent of these TUs were localized to subtelomeric and pericentromeric regions, implicating these regions in the creation of new species-specific genes.
Finally, a study led in part by the Broad Institute's John Rinn followed up on previous work that discovered lincRNAs (large intergenic noncoding RNAs), finding that many of them aggregate with chromatin-modifying complexes to alter gene expression. They observed, by looking at chromatin-state maps, that the number of human lincRNAs is actually 3,300 and about 20 percent of these are bound by the polycomb repressive complex (PRC)2. By knocking out certain lincRNAs associated with (PRC)2 using siRNAs, they saw up-regulation of gene expression by those genes normally silenced by (PRC)2.