Single Nucleotide Polymorphisms Associated with Reading Ability Show Connection to Socio-Economic Outcomes.

Impairments in reading and in language have negative consequences on life outcomes, but it is not known to what extent genetic effects influence this association. We constructed polygenic scores for difficulties with language and learning to read from genome-wide data in ~6,600 children, adolescents and young adults, and tested their association with health, socioeconomic outcomes and brain structure measures collected in adults (maximal N = 111,749). Polygenic risk of reading difficulties was associated with reduced income, educational attainment, self-rated health and verbal-numerical reasoning (p < 0.00055). Polygenic risk of language difficulties predicted income (p = 0.0005). The small effect sizes ranged 0.01-0.03 of a standard deviation, but these will increase as genetic studies for reading ability get larger. Polygenic scores for childhood cognitive ability and educational attainment were correlated with polygenic scores of reading and language (up to 0.09 and 0.05, respectively). But when they were included in the prediction models, the observed associations between polygenic reading and adult outcomes mostly remained. This suggests that the pathway from reading ability to social outcomes is not only via associated polygenic loads for general cognitive function and educational attainment. The presence of non-overlapping genetic effect is indicated by the genetic correlations of around 0.40 (childhood intelligence) and 0.70 (educational attainment) with reading ability. Mendelian randomization approaches will be important to dissociate any causal and moderating effects of reading and related traits on social outcomes.

An aqueous orally active vaccine targeted against a RAGE/AB complex as a novel therapeutic for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that gradually destroys a person's memory. Substantial evidence suggests that amyloid beta (Aß) and the receptor for advanced glycation endproducts (RAGE) play an important and often deleterious role in the pathogenesis of AD. RAGE facilitates the translocation of Aß from the periphery into the brain, mediates the Aß-induced neurotoxicity, and enhances the release of pro-inflammatory cytokines increasing the inflammatory response. In addition, soluble forms of RAGE (sRAGE) and Aß bind together in the periphery forming high molecular weight complexes that are more highly immunogenic and less neurotoxic than Aß1-42 alone. We show here that there are elevated anti-RAGE and anti-Aß titers (in a near 1:1 relationship) in samples analyzed from human AD patients, aged non-human primates, and AD transgenic mice (APPSWE-PS1). We show that an in vitro prepared RAGE/Aß complex induces a greater immunogenic response (increased anti-Aß1-42 and anti-RAGE antibody titers) in both human peripheral blood mononuclear cells (PBMCs) and immunized Balb-C mice than does either Aß1-42 or RAGE alone. Further, pretreatment with endogenous anti-RAGE antibodies isolated from our transgenic APPSWE-PS1 mice can prevent Aß1-42-induced neurotoxicity in cultured primary rat cortical neurons. Finally, we examine the effectiveness of an orally administered vaccine of either RAGE/Aß complex or Aß1-42 alone in improving cognitive function in our AD transgenic mice. Our results to date support the hypothesis that a protein complex vaccine that targets both RAGE and Aß1-42 will provide a more effective treatment for AD than vaccination with Aß1-42 alone.