Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.

BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data. METHOD: The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized. RESULTS: This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau. CONCLUSIONS: Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.

17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression.

To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers. However, amyloid positon emission tomography (PET) imaging, performed in three patients, was negative. Analysis of an additional case with neuropathological examination confirmed that the MAPT duplication causes a complex tauopathy, including prominent neurofibrillary tangle pathology in the medial temporal lobe without amyloid-ß deposits. 17q21.31 duplication is the genetic basis of a novel entity marked by prominent tauopathy, leading to early-onset dementia with an AD clinical phenotype. This entity could account for a proportion of probable AD cases with negative amyloid PET imaging recently identified in large clinical series.

Isolasion, identification and antimicrobial resistance patterns of Salmonella from meat products in Tehran.

The present study was carried out from 400 samples in different slaughterhouses to report the isolation along with the serotypes and antibiogram pattern of Salmonella among products in Tehran. Salmonella was isolated from samples of chicken, beef; veal, mutton, roast beef and sausage fermentive meat collected at slaughterhouses. The isolates were characterized by serotyping and antimicrobial-susceptibility testing. Eighty isolates of Salmonella enterica belonging to 19 serotypes--S. adelaide, S. agona S. abortus ovis, S. abortus bovis, S. derby, S. dublin, S. enteritidis, S. havana, S. heidelberg, S. indiana, S. infantis, S. kentucky, S. montevideo, S. newport, S. saint paul, S. senftenberg, S. typhimurium, S. thompson, S. worthington were obtained with an overall prevalence of 20%. The most strains of Salmonella enterica were isolated from roast beef. S. enterica serotype Thompson and S. enterica serotype typhimurium were isolated most frequently. All of the isolates were resistant to at least one antibiotic and 94% were resistant to at least three antibiotics. Six% were resistant to ceftriaxone, the drug of choice for treating salmonellosis in children. One isolates of S. enterica serotype infantis had resistance to 15 antibiotics and the one isolate of serotype Thompson and one isolate of Serotype havana were resistant to 14 antibiotics. Norfloxacin, cefteriaxone and cefotaxime were most effective, whereas, erythromycin, tetracycline, nalidixic acid, furazolidone and nitrofurantoin were relatively less effective. Resistant strains of Salmonella are common in meat products. These finding provide support for adoption of guidelines for the prudent use of antibiotics in food animals and for a reduction in the number of pathogens present on farms and slaughterhouses. Thus, it is imperative that salmonellosis control measures adopted for humans should give adequate importance to its control in animals particularly their products.