Provocative research combining multiscale network analysis of viromic, genomic, transcriptomic, and histopathologic data from four key brain regions advances the theory of “viral activity constituting a general feature of Alzheimer’s disease,” according to the investigators (Neuron 2018;99:1-19). Specifically, a consortium of research teams funded by the National Institute on Aging Accelerating Medicines Partnership-Alzheimer’s Disease found two common Roseoloviruses—human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7)—were at levels up to twice as high in post-mortem brain tissue of individuals with Alzheimer’s disease than in those without, findings consistent across three independent cohorts.
The researchers also analyzed large data sets of viral DNA and RNA along with networks of human genes associated with Alzheimer’s disease and with regulation of amyloid beta, a key protein involved in Alzheimer’s pathology. The authors found HHV-6A and HHV-7 associated with perturbations in the expression of these human genes and genetic transcription factors. In addition, they noted that HHV-6A suppressed miR-155, a microRNA that regulates adaptive and innate immune responses.
Based on the latter finding, the researchers depleted miR-155 in mice and found they developed amyloid plaques and behavior changes.
The overall project started when the investigators constructed, mapped, and compared differences in gene regulatory networks from RNA sequencing data from 622 post-mortem brain samples of individuals with and without Alzheimer’s disease. This pointed to a possible role of viral mediators in Alzheimer’s disease, which led to a second analysis of 800 additional sequencing samples collected at separate institutions. This second analysis confirmed persistently higher abundance of HHV-6A and HHV-7 out of more than 500 viral species quantified in samples from individuals with Alzheimer’s disease in comparison to samples from individuals who were cognitively normal.
The authors emphasized that their findings do not establish HHV-6A or HHV-7 as a cause of Alzheimer’s disease. Rather, they noted, the disease’s “biology is impacted by a complex constellation of viral and host factors acting across different timescales and physiological systems.”
Only One-Third of Most Common Personal Use Blood Glucose Meters Met Accuracy Standards
A study of 18 blood glucose meters (BGMs) cleared for personal use that accounted for about 90% of purchases from consumer outlets between 2013 and 2015 found that just six met a predefined accuracy standard on three of three studies, while four did not meet this standard on any of the studies (Diab Care 2018; doi.org/10.2337/dc17-1960). These findings could assist patients, professionals, and payers in choosing BGMs and regulators in evaluating postclearance BGM performance, according to the authors.
The investigators purchased the BGMs from retail pharmacies and online retailers. They recruited for testing at three clinical sites 1,035 subjects with type 1 diabetes, type 2 diabetes, prediabetes, or normal glycemia. Participants had their fingerstick capillary blood sampled and measured with six BGMs and gave reference plasma samples by deep finger puncture for processing at a reference laboratory.
The investigators evaluated BGM accuracy against a standard of reported values being within 15% of a reference plasma value ≥100 mg/dL and within 15 mg/dL of a reference value <100 mg/dL, which is less stringent than the standard issued by the Food and Drug Administration in 2016. They also assessed the BGMs across four other accuracy measures.
The six BGMs that met the accuracy standard also performed the best on meeting the four other accuracy measures. There was a wide range of performance among the 12 BGMs that didn’t meet the accuracy standard in all three studies and on the other four measures.
The investigators noted that since testing performed by professionals tends to be more accurate than when individuals test themselves, the accuracy results reported in this study could be higher than what might be experienced in actual use.
Three Common Blood Tests Could be Used to Screen for Obstructive Sleep Apnea
Elevated levels of three common blood tests—HbA1c, C-reactive protein (CRP), and erythropoietin (EPO)—“should generate a high level of suspicion of obstructive sleep apnea [OSA] and may have utility as an OSA screening tool” in adult men, according to the authors (Nat Sci Sleep 2018;10:159-67). The findings are from a multicenter prospective study of 264 men with clinically suspected OSA who underwent overnight sleep studies and clinical evaluations, including completion of two OSA screening tools.
These results validate the investigators’ prior feasibility study examining the association of 11 biomarkers with clinical suspicion of OSA. In this validation study, the authors assessed the performance of five biomarkers, including HbA1c, CRP, EPO, interleukin-6, and uric acid. They found that HbA1c, CRP, and EPO had statistically significant correlations with OSA severity indices, and in combination had an area under the receiver operating characteristic (AUROC) of 0.78, which was superior to two OSA screening tools, the Epworth Sleepiness Scale (ESS) (0.53) and STOP-Bang (0.70).
The authors also looked at the sensitivity, specificity, positive predictive value, and negative predictive value of the analytes individually and in combination in detecting OSA. Using cutoffs of 5.7%, 0.2 mg/dL, and 8 mIU/mL, sensitivity and specificity of HbA1c, CRP, and EPO were 38%/88%, 52%/77%, and 66%/58%, respectively. Considering these biomarkers in combination according to a weighted linear formula yielded sensitivity and specificity of 81% and 60%, respectively. In contrast the sensitivity of body mass index, ESS, and neck circumference was 64%, 53%, 44%, respectively. Sensitivity of STOP-Band was 91% using a 3 cutoff and 44% with a 5 cutoff.