Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Mortalidade por doença meningocócica no Município de São Paulo, Brasil: características e preditores

O estudo objetiva descrever a magnitude, as caracter&#237;sticas da mortalidade e da letalidade por doen&#231;a meningoc&#243;cica e investigar preditores de &#243;bito por essa causa, no Munic&#237;pio de S&#227;o Paulo, Brasil, de 1986 a 2004. Utilizou-se a regress&#227;o log&#237;stica m&#250;ltipla n&#227;o condicional para a investiga&#231;&#227;o dos preditores de &#243;bitos. Foram estudados 10.087 casos de doen&#231;a meningoc&#243;cica no munic&#237;pio. A taxa anual m&#233;dia de mortalidade foi de 1,0/100 mil habitantes/ano, variando de 0,2 a 1,8; a letalidade foi de 20,5% com grandes diferen&#231;as segundo idade, sorogrupo e tipo de hospital. Os preditores de &#243;bito por doen&#231;a meningoc&#243;cica foram idade, especialmente as faixas et&#225;rias de um a dois anos e de 40 anos ou mais e o sorogrupo W. Os resultados obtidos podem contribuir para a elabora&#231;&#227;o de pol&#237;ticas p&#250;blicas com foco na organiza&#231;&#227;o da assist&#234;ncia hospitalar e elabora&#231;&#227;o de protocolos que promovam a maior efetividade do tratamento e a aplica&#231;&#227;o de estrat&#233;gias de vacina&#231;&#227;o que diminuam a incid&#234;ncia nos grupos de maior risco para &#243;bito por doen&#231;a meningoc&#243;cica

Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma

Inflammation and asthma have both been reported in some children with autism spectrum disorder (ASD). To further assess this connection, peripheral immune cells isolated from young children with ASD and typically developing (TD) controls and the production of cytokines IL-17, −13, and −4 assessed following ex vivo mitogen stimulation. Notably, IL-17 production was significantly higher following stimulation in ASD children compared to controls. Moreover, IL-17 was increased in ASD children with co-morbid asthma compared to controls with the same condition. In conclusion, children with ASD exhibited a differential response to T cell stimulation with elevated IL-17 production compared to controls