Physical activity protects brain function in healthy individuals and those with Alzheimer's disease (AD). Evidence for beneficial effects of parental exercise on the health status of their progeny is sparse and limited to nondiseased individuals. Here, we questioned whether maternal running interferes with offspring's AD‐like pathology and sought to decipher the underlying mechanisms in TgCRND8 mice. Maternal stimulation was provided by voluntary wheel running vs . standard housing during pregnancy. Following 5 mo of standard housing of transgenic and wild‐type offspring, their brains were examined for AD‐related pathology and/or plasticity changes. Running during pregnancy reduced β‐amyloid (Aβ) plaque burden (–35%, P = 0.017) and amyloidogenic APP processing in transgenic offspring and further improved the neurovascular function by orchestrating different Aβ transporters and increasing angiogenesis (+29%, P =0.022). This effect was accompanied by diminished inflammation, as indicated by reduced microgliosis (–20%, P =0.002) and down‐regulation of other proinflammatory mediators, and resulted in less oxidative stress, as nitrotyrosine levels declined (–28%, P =0.029). Moreover, plasticity changes (in terms of up‐regulation of reelin, synaptophysin, and ARC) were found not only in transgenic but also in wild‐type offspring. We conclude that exercise during pregnancy provides long‐lasting protection from neurodegeneration and improves brain plasticity in the otherwise unstimulated progeny.—Herring, A., Donath, A., Yarmolenko, M., Uslar, E., Conzen, C., Kanakis, D., Bosma, C., Worm, K., Paulus, W., Keyvani, K. Exercise during pregnancy mitigates Alzheimer‐like pathology in mouse offspring. FASEB J. 26, 117–128 (2012). www.fasebj.org

Alterations in the expression of Reelin (RELN) have been implicated in the pathology of Alzheimer's disease (AD). However, whether these changes are cause or consequence of AD remains to be resolved. To better understand the role of RELN pathway in t

Aims: DNA methylation‐based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour.Patients and methods: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the ‘conumee’ package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed.Results: Genome‐wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation‐defined variant of low‐grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities.Conclusions: DNA methylation‐based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation‐defined class of low‐grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma‐like features and nuclear clusters.