An increasing number of studies argues that self-propagating protein conformations (i.e., prions) feature in the pathogenesis of several common neurodegenerative diseases. Mounting evidence contends that aggregates of the amyloid-β (Aβ) peptide become self-propagating in Alzheimer's disease (AD) patients. An important characteristic of prions is their ability to replicate distinct strains, the biological information for which is enciphered within different conformations of protein aggregates. To investigate whether distinct strains of Aβ prions can be discerned in AD patients, we performed transmission studies in susceptible transgenic mice using brain homogenates from sporadic or heritable (Arctic and Swedish) AD cases. Mice inoculated with the Arctic AD sample exhibited a pathology that could be distinguished from mice inoculated with the Swedish or sporadic AD samples, which was judged by differential accumulation of Aβ isoforms and the morphology of cerebrovascular Aβ deposition. Unlike Swedish ADor sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent Aβ38-containing cerebral amyloid angiopathy. The divergent transmission behavior of the Arctic AD sample compared with the Swedish and sporadic AD samples was maintained during second passage in mice, showing that Aβ strains are serially transmissible. We conclude that at least two distinct strains of Aβ prions can be discerned in the brains of AD patients and that strain fidelity was preserved on serial passage in mice. Our results provide a potential explanation for the clinical and pathological heterogeneity observed in AD patients.neurodegeneration | bioluminescence imaging | seeding | proteinopathies

We have shown for the first time that PLR is a novel independent prognostic marker in patients with ovarian cancer.

This paper investigated the predictive ability of expressive vocabulary size and lexical composition at age 2 on later language and literacy skills from ages 3 through 11. Multivariate analysis of covariance was performed to compare 16 language and literacy outcomes between children with large expressive vocabulary size at 24 months (N = 1,073) and those with smaller expressive vocabulary size. Comparisons between large and small verb size groups as a measure of lexical composition were also conducted. Our findings indicate that, after controlling for gender, birth order, ethnicity and socioeconomic status, total vocabulary size at age 2 can significantly predict subsequent language and literacy achievement up to fifth grade. Moreover, vocabulary size is a better predictor of later language ability than lexical composition.

The study provides evidence that the risk of cancers common in Western countries is higher for Korean Americans than for their native counterparts. Recent trends among Korean Americans also revealed a stronger Western profile.

Martin Gallagher and colleagues examine the long-term outcomes of renal replacement therapy (RRT) dosing in patients with acute kidney injury randomized to normal vs. augmented RRT.Please see later in the article for the Editors' Summary