News briefs

Alzheimer gene a double whammy

An international team, including researchers from the University of Melbourne, has found that a gene called ApoE4, known to be associated with an increased risk of developing Alzheimer disease, also influences the harmful accumulation of tau protein in the brains of mice. ApoE4 influences the deposition of amyloid-β, the protein that forms plaques in the brains of patients with Alzheimer disease, but this study, published in Nature, is the first to show that the gene also influences tau pathology, another major signature of the disease. ApoE4 was identified as a strong genetic risk factor for late-onset Alzheimer disease in 1993, but the mechanisms underlying its contribution to the pathology of the disease remain poorly understood. Using a mouse model of tauopathy (a condition in which tau aggregates as tangles in the brain), the researchers showed that the ApoE4 protein influences tau pathogenesis, and increases neuroinflammation and tau-mediated neurodegeneration, independent of amyloid-β pathology. They found that in mice ApoE4 exerts a toxic gain of function on these processes, whereas its absence seems to be protective, attenuating tau-mediated neuroinflammation and neurodegeneration. Further work is needed to determine whether the findings can be translated to the clinic, but the study suggests that ApoE4 may be a promising therapeutic target for reducing tau-associated neurodegeneration.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature24016.html

Parental age influences new genetic mutations in children

Older parents, and especially older fathers, tend to have children with a greater number of DNA mutations, according to research published in Nature. The researchers examined the DNA of more than 1500 families in Iceland to see how frequently DNA changes occurred in each generation and how the parents’ age affected those changes. Such changes in DNA are a key driver of evolution as well as a source of rare genetic diseases, and arise during the formation of eggs and sperm. The researchers analysed the whole genome sequence data for 1548 Icelanders, their parents, and, for a subset of 225 of these individuals, at least one of their children, with the aim of understanding how the age and sex of the parents influence the number of de novo genetic mutations (DNMs). The authors identified 108 778 high quality DNMs, an average of 70.3 DNMs per family. Further, they found that the number of DNMs from mothers increased by 0.37 per year of age, one-quarter of the 1.51 per year of age attributable to fathers. However, they also found that the number of clustered mutations increased more rapidly with the mother’s age than with the father’s, and the genomic span of maternal DNM clusters was greater than that of paternal changes. In addition, the types of DNMs from mothers changed substantially with age.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature24018.html