Ultrastructural changes in cerebral capillary pericytes in aged Notch3 mutant transgenic mice.

Pericytes, the specialized vascular smooth muscle cells (VSMCs), play an important role in supporting and maintaining the structure of capillaries. Pericytes show biochemical and physiologic features similar to VSMC, usually containing smooth muscle actin fibers and rich endoplasm reticulum. Studies have indicated that degeneration of VSMCs due to Notch3 mutations is the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Toward a multifactorial model of Alzheimer disease.

Relations among antecedent biomarkers of Alzheimer disease (AD) were evaluated using causal modeling; although correlation cannot be equated to causation, causation does require correlation. Individuals aged 43 to 89 years (N = 220) enrolled as cognitively normal controls in longitudinal studies had clinical and psychometric assessment, structural magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarkers, and brain amyloid imaging via positron emission tomography with Pittsburgh Compound B (PIB) obtained within 1 year. CSF levels of Aβ(42) and tau were minimally correlated, indicating they represent independent processes.

11C-PiB imaging of human immunodeficiency virus-associated neurocognitive disorder.

Objective: To evaluate whether the amyloid-binding agent carbon 11-labeled Pittsburgh Compound B ((11)C-PiB) could differentiate Alzheimer disease (AD) from human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) in middle-aged HIV-positive participants.

Design: (11)C-PiB scanning, clinical assessment, and cerebrospinal fluid (CSF) analysis were performed. Both χ(2) and t tests assessed differences in clinical and demographic variables between HIV-positive participants and community-living individuals observed at the Knight Alzheimer's Disease Research Center (ADRC).

Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition.

Objective: APOE ε4 status has been associated with greater cortical amyloid deposition, whereas exercise has been associated with less in cognitively normal adults. The primary objective here was to examine whether physical exercise moderates the association between APOE genotype and amyloid deposition in cognitively normal adults.

Design: APOE genotyping data and answers to a questionnaire on physical exercise engagement over the last decade were obtained in conjunction with cerebrospinal fluid (CSF) samples and amyloid imaging with carbon 11-labeled Pittsburgh Compound B ([(11)C]PiB) positron emission tomography.

Cerebrospinal fluid proteins predict longitudinal hippocampal degeneration in early-stage dementia of the Alzheimer type.

Objective: Biomarkers are needed to improve the sensitivity and accuracy of diagnosis, and also prognosis, in individuals with early Alzheimer disease (AD). Measures of brain structure and disease-related proteins in the cerebrospinal fluid (CSF) have been proposed as biomarkers, yet relatively little is known about the relationships between such measures. The present study was conducted to assess the relationship between CSF Aβ and tau protein levels and longitudinal measures of hippocampal structure in individuals with and without very mild dementia of the Alzheimer type.

Altered inhibition of negative emotions in subjects at family risk of major depressive disorder.

Unaffected 1st degree relatives of patients with major depressive disorder (MDD) are more likely to develop MDD than healthy controls. The aim of our study was to establish neuronal correlates of familial susceptibility in the process of inhibition of emotional information. Unaffected 1st degree relatives of patients with MDD (N = 21) and matched healthy controls (N = 25) underwent a functional magnetic resonance imaging procedure with an inhibition task.

Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine-resistant breast cancer.

The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity that permits the emergence of a hormone-independent tumor. The steroid coactivator protein SRC-1, through interactions with developmental proteins and other nonsteroidal transcription factors, drives this tumor adaptability. In this discovery study, we identified ADAM22, a non-protease member of the ADAM family of disintegrins, as a direct estrogen receptor (ER)-independent target of SRC-1.

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression.

Background: Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes.

Methods: Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions.

Role of family history for Alzheimer biomarker abnormalities in the adult children study.

Objective: To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities.

Design: Adult Children Study.

Setting: Washington University's Charles F.

Donepezil impairs memory in healthy older subjects: behavioural, EEG and simultaneous EEG/fMRI biomarkers.

Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants.

Cerebrospinal fluid biomarkers, education, brain volume, and future cognition.

Background: Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size.

Objective: To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid(42) (Aβ(42)), tau, and phosphorylated tau (ptau(181)) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment.

Design: Longitudinal cohort study.

Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease.

Background: Apolipoprotein E (APOE) is the most statistically significant genetic risk factor for late-onset Alzheimer disease (LOAD). The linkage disequilibrium pattern around the APOE gene has made it difficult to determine whether all the association signal is derived from APOE or whether there is an independent signal from a nearby gene.

Objective: To attempt to replicate a recently reported association of APOE 3-TOMM40 haplotypes with risk and age at onset.

Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.

Objective: There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer's disease (AD) pathology in cognitively normal individuals because it is in this population that disease-modifying therapies may have the greatest chance of success. While AD pathology is estimated to begin ~10-15 years prior to the onset of cognitive decline, substantial neuronal loss is present by the time the earliest signs of cognitive impairment appear. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury.

Gender differences in the effects of exposure to intimate partner violence on adolescent violence and drug use.

Objective: This study investigated the long-term effects of exposure to intimate partner violence in the home on adolescent violence and drug use and gender differences in these relationships. Although the general relationship between exposure to IPV and negative outcomes for youth has been demonstrated in past research, gender differences in the effects of IPV on adolescents have been rarely assessed using longitudinal data.

Methods: Longitudinal data was obtained from 1,315 adolescents and their primary caregivers participating in the Project on Human Development in Chicago Neighborhoods (PHDCN).

Sustaining the utilization and high quality implementation of tested and effective prevention programs using the communities that care prevention system.

This paper describes the extent to which communities implementing the Communities That Care (CTC) prevention system adopt, replicate with fidelity, and sustain programs shown to be effective in reducing adolescent drug use, delinquency, and other problem behaviors. Data were collected from directors of community-based agencies and coalitions, school principals, service providers, and teachers, all of whom participated in a randomized, controlled evaluation of CTC in 24 communities. The results indicated significantly increased use and sustainability of tested, effective prevention programs in the 12 CTC intervention communities compared to the 12 control communities, during the active phase of the research project when training, technical assistance, and funding were provided to intervention sites, and 2 years following provision of such resources.

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.

Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability.

Human apoE isoforms differentially regulate brain amyloid-β peptide clearance.

The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset, sporadic Alzheimer's disease (AD). The APOE ε4 allele markedly increases AD risk and decreases age of onset, likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. In contrast, the APOE ε2 allele appears to decrease AD risk.

Alternative processing of γ-secretase substrates in common forms of mild cognitive impairment and Alzheimer's disease: evidence for γ-secretase dysfunction.

Objective: The most common pathogenesis for familial Alzheimer's disease (FAD) involves misprocessing (or alternative processing) of the amyloid precursor protein (APP) by γ-secretase due to mutations of the presenilin 1 (PS1) gene. This misprocessing/alternative processing leads to an increase in the ratio of the level of a minor γ-secretase reaction product (Aβ42) to that of the major reaction product (Aβ40). Although no PS1 mutations are present, altered Aβ42/40 ratios are also observed in sporadic Alzheimer's disease (SAD), and these altered ratios apparently reflect deposition of Aβ42 as amyloid.

Regional and temporal variations in tissue sodium concentration during the acute stroke phase.

A technique for noninvasively quantifying the concentration of sodium ((23) Na) ions was applied to the study of ischemic stroke. (23) Na-magnetic resonance imaging techniques have shown considerable potential for measuring subtle changes in ischemic tissue, although studies to date have suffered primarily from poor signal/noise ratio. In this study, accurate quantification of tissue sodium concentration (TSC) was achieved in (23) Na images with voxel sizes of 1.

Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology.

Background: Cerebrospinal fluid (CSF) biomarkers of Alzheimer disease (AD) are currently being considered for inclusion in revised diagnostic criteria for research and/or clinical purposes to increase the certainty of antemortem diagnosis.

Objective: To test whether CSF biomarker assays differ in their ability to identify true markers of underlying AD pathology (eg, amyloid plaques and/or neurofibrillary tangles) in living individuals.

Design: We compared the performances of the 2 most commonly used platforms, INNOTEST enzyme-linked immunosorbent assay and INNO-BIA AlzBio3, for measurement of CSF β-amyloid (Aβ) and tau proteins to identify the presence of amyloid plaques in a research cohort (n=103).

Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer's disease diagnosis and prognosis.

Background: Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181).

Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.

The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia.

How Do Families Matter? Age and Gender Differences in Family Influences on Delinquency and Drug Use.

Parenting practices, age, and gender all influence adolescent delinquency and drug use, but few studies have examined how these factors interact to affect offending. Using data from 18,512 students in Grades 6, 8, 10 and 12, this study found that across grades, parents treated girls and boys differently, but neither sex received preferential treatment for all practices assessed, and younger children reported more positive parenting than older students. Family factors were significantly related to delinquency and drug use for both sexes and for all grades.

Development of a vessel-mimicking material for use in anatomically realistic Doppler flow phantoms.

Polyvinyl alcohol cryogel (PVA-C) is presented as a vessel-mimicking material for use in anatomically realistic Doppler flow phantoms. Three different batches of 10% wt PVA-C containing (i) PVA-C alone, (ii) PVA-C with antibacterial agent and (iii) PVA-C with silicon carbide particles were produced, each with 1-6 freeze-thaw cycles. The resulting PVA-C samples were characterized acoustically (over a range 2.