Nonlinear Z-score modeling for improved detection of cognitive abnormality.

Introduction: Conventional Z-scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these "adjusted" Z-scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z-scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.

The longitudinal evaluation of familial frontotemporal dementia subjects protocol: Framework and methodology.

Introduction: It is important to establish the natural history of familial frontotemporal lobar degeneration (f-FTLD) and provide clinical and biomarker data for planning these studies, particularly in the asymptomatic phase.

Methods: The Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects protocol was designed to enroll and follow at least 300 subjects for more than at least three annual visits who are members of kindreds with a mutation in one of the three most common f-FTLD genes-microtubule-associated protein tau, progranulin, or chromosome 9 open reading frame 72.

Results: We present the theoretical considerations of f-FTLD and the aims/objectives of this protocol.

Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis.

Importance: An increasingly varied clinical spectrum of cases with amyotrophic lateral sclerosis (ALS) has been identified, and objective criteria for clinical trial eligibility are necessary.

Objective: To develop a cerebrospinal fluid (CSF) biomarker sensitive and specific for the diagnosis of ALS.

Design, Setting, And Participants: A case-control study including 51 individuals with ALS and 23 individuals with a disorder associated with a 4-repeat tauopathy was conducted at an academic medical center.

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts.

Biochemical markers in Alzheimer's disease clinical trials.

This article summarizes how biochemical markers may aid in the development of novel treatments that interfere with fundamental pathogenic processes in Alzheimer's disease. Details are given on the potential use of biomarkers in Alzheimer's disease clinical trials as additional inclusion criteria to enrich study populations with participants who really suffer from the disease, as a means to stratify study participants into meaningful subgroups that may benefit differently from the treatment, and as tools to detect desired biochemical effects and undesired side effects of the drug.

Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer's disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients.

A potential new pathway for Staphylococcus aureus dissemination: the silent survival of S. aureus phagocytosed by human monocyte-derived macrophages.

Although considered to be an extracellular pathogen, Staphylococcus aureus is able to invade a variety of mammalian, non-professional phagocytes and can also survive engulfment by professional phagocytes such as neutrophils and monocytes. In both of these cell types S. aureus promptly escapes from the endosomes/phagosomes and proliferates within the cytoplasm, which quickly leads to host cell death.

sigmaB modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4.

The accessory sigma factor sigmaB controls a general stress response that is thought to be important for Staphylococcus aureus survival and may contribute to virulence. The strain of choice for genetic studies, 8325-4, carries a small deletion in rsbU, which encodes a positive regulator of sigmaB activity. Consequently, to enable the role of sigmaB in virulence to be addressed, we constructed an rsbU(+) derivative, SH1000, using a method that does not leave behind an antibiotic resistance marker.