Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer's disease.

The roles of APOEε4 and APOEε2-the strongest genetic risk and protective factors for Alzheimer's disease-in glial responses remain elusive. We tested the hypothesis that APOE alleles differentially impact glial responses by investigating their effects on the glial transcriptome from elderly control brains with no neuritic amyloid plaques. We identified a cluster of microglial genes that are upregulated in APOEε4 and downregulated in APOEε2 carriers relative to APOEε3 homozygotes. This microglia-APOE cluster is enriched in phagocytosis-including TREM2 and TYROBP-and proinflammatory genes, and is also detectable in brains with frequent neuritic plaques. Next, we tested these findings in APOE knock-in mice exposed to acute (lipopolysaccharide challenge) and chronic (cerebral ß-amyloidosis) insults and found that these mice partially recapitulate human APOE-linked expression patterns. Thus, the APOEε4 allele might prime microglia towards a phagocytic and proinflammatory state through an APOE-TREM2-TYROBP axis in normal aging as well as in Alzheimer's disease.

Extraversion degrades performance on the antisaccade task.

Previous studies have suggested that baseline and task-related activity within the prefrontal cortex varies with the degree of extraversion; we examined whether this trait influenced performance on the antisaccade task, a measure commonly used in psychiatric and neurological disorders. Extraversion was assessed in young normal subjects using the Eysenck Personality Questionnaire-Revised Short-scale. Highly extraverted and highly introverted subjects' antisaccade errors and latencies were evaluated. Extraversion was associated with significantly more errors but did not influence the latency of either correct or erroneous responses. This effect on error rate but not latency is similar to that seen in schizotypal personality disorder, whereas normal ageing, as well as schizophrenia and attention deficit-hyperactivity disorder, increase errors and also delay saccade onset. This is the first study in a young, non-clinical population to show an influence of a normal personality dimension on an ocular motor measure.