Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

Bell, R.D. et al. Nature doi:10.1038/nature11087 (16 May).

The authors provide a mechanistic link between the APOE4 gene and blood-brain–barrier defects by showing that APOE4 expression in mice activates a pathway in pericytes involving cyclophilin A (CypA) activation. This leads to neuronal uptake of blood-derived neurotoxic proteins. Thus, CypA may be a potential target for treating APOE4-mediated neurovascular injury, such as in Alzheimer's disease.

PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue T reg cells

Cipolletta, D. et al. Nature doi:10.1038/nature11132 (16 May).

This study uncovers a new aspect to the action of the thiazolidinedione drug pioglitazone, used in the treatment of type 2 diabetes. The authors show that a population of regulatory T cells in the visceral fat are controlled by peroxisome proliferator–activated receptor γ (PPAR-γ) and that the expression of PPAR-γ in these cells is important for the insulin-sensitizing activity of pioglitazone.

Detectable clonal mosaicism and its relationship to aging and cancer

Jacobs, K.B. et al. Nat. Genet. doi:10.1038/ng.2270 (6 May).

Detectable clonal mosaicism from birth to old age and its relationship to cancer

Laurie, C.C. et al. Nat. Genet. doi:10.1038/ng.2271 (6 May).

Two new studies find mosaicism for large chromosomal abnormalities in peripheral blood samples from individuals in the general population. The frequency of these genetic changes increases with age and is associated with an increased risk of subsequently developing a hematological cancer.

Adolescent impulsivity phenotypes characterized by distinct brain networks

Whelan, R. et al. Nat. Neurosci. doi:10.1038/nn.3092 (29 April).

The authors examine the activation of brain networks in adolescents with attention-deficit hyperactivity disorder (ADHD) and those who had used drugs or alcohol using functional magnetic resonance imaging. They find that although both ADHD and substance abuse are associated with increased impulsiveness, different brain networks were activated in response to a task testing impulsiveness in these two contexts.