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[This corrects the article DOI: 10.1371/journal.pone.0193961.].

The original version of this article [1] unfortunately contained a typographical error. The 'Alzheimer's Disease Neuroimaging Initiative' was erroneously included as 'Alzheimer's Disease Neuroimaging Initative' in the author list of the article.

This study shows that variants in TREM2 are a rare cause of Alzheimer's disease and underscores the role of the microglial cell in the disease mechanism and as a potential target for therapy. Alzheimer's disease is the most common cause of dementia, typically presenting with a progressive loss of cognitive function and memory. It is a complex disorder with a strong genetic component. In the past, genetic studies have identified mutations in three genes — APP (encoding amyloid precursor protein), PSEN1 (encoding presenilin 1), and PSEN2 (encoding presenilin 2) — as the cause of disease in several families, most of whom have early-onset disease. Expansions in C9orf72 are found in families with mixed types of disease. In late-onset disease, the most common form of Alzheimer's disease, the ε4 allele of the apolipoprotein E . . .

Brain cytotoxic edema is a neuroradiological sign secondary to variegate diseases ranging from migraine to fulminant Listeria rhombencephalitis. The tempestive identification of its underlying cause is vital for an effective treatment as any delay may be fatal. However, the lack of distinctive imaging biomarkers and the paucity of reports pose a significant challenge in its diagnosis and frequently lead to a misdiagnosis particularly with the more common acute ischemic stroke. Importantly, due to its rarity, mesencephalon midline cytotoxic lesion is likely to remain an underdiagnosed clinical phenomenon, especially if follow up MRI is not performed. Here we report a case of a central, midline, symmetric midbrain cytotoxic edema in a haemodialysis patient with diverse chronic progressive severe cardiovascular risk factors and a newly diagnosed atrial fibrillation. We expand the spectrum of neuroradiological hallmarks associated to terminal renal failure and report a full moon-like mesencephalon midline transient restricted diffusion as a reliable imaging biomarker for the prompt and accurate diagnosis of midbrain cytotoxic edema with the enormous potential of rapidly identifying and effectively treating its causative factors and timely reverse the associated symptomatic.

Whole-exome sequencing reveals that a rare variant of phospholipase D3 ( PLD3 ( V232M )) segregates with Alzheimer’s disease status in two independent families and doubles risk for the disease in case–control series, and that several other PLD3 variants increase risk for Alzheimer’s disease in African Americans and people of European descent. New genetic risk variant for Alzheimer's disease The identification of mutations causing Alzheimer's disease in amyloid-β precursor protein, presenilin 1 and presenilin 2 led to a better understanding of the pathobiology of the condition. Further mutations are expected to be implicated, but the identification of such variants has been challenging. These authors used exome sequencing to identify low-frequency coding variants with large effects on late-onset Alzheimer's disease. They report several coding variants in the gene PLD3 , coding for phospholipase D3, that increase disease risk at least twofold. PLD3 may have a role in the processing of amyloid-β and may have potential as a novel therapeutic target. Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD) 1 , 2 . These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer’s disease in seven independent case–control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3 , reveal that several variants in this gene increase risk for Alzheimer’s disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.