Regional Differences in Microbial Infiltration of Brain Tissue from Alzheimer's Disease Patients and Control Individuals.

Alzheimer's disease (AD) is characterized by cognitive decline and neuropathology including amyloid beta (Aβ) plaques and neurofibrillary tangles (tau). Factors initiating or driving these pathologies remain unclear, though microbes have been increasingly implicated. Our data and others' findings indicate that microbes may be common constituents of the brain.

Metabolic Profiling of Neocortical Tissue Discriminates Alzheimer's Disease from Mild Cognitive Impairment, High Pathology Controls, and Normal Controls.

Alzheimer's disease (AD) is the most common cause of dementia, accounting for an estimated 60-80% of cases, and is the sixth-leading cause of death in the United States. While considerable advancements have been made in the clinical care of AD, it remains a complicated disorder that can be difficult to identify definitively in its earliest stages. Recently, mass spectrometry (MS)-based metabolomics has shown significant potential for elucidation of disease mechanisms and identification of therapeutic targets as well diagnostic and prognostic markers that may be useful in resolving some of the difficulties affecting clinical AD studies, such as effective stratification.

Clearing, immunofluorescence, and confocal microscopy for the three-dimensional imaging of murine testes and study of testis biology.

Optical clearing techniques provide unprecedented opportunities to study large tissue samples at histological resolution, eliminating the need for physical sectioning while preserving the three-dimensional structure of intact biological systems. There is significant potential for applying optical clearing to reproductive tissues. In testicular biology, for example, the study of spermatogenesis and the use of spermatogonial stem cells offer high-impact applications in fertility medicine and reproductive biotechnology.

Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers.

The APOE gene, encoding apolipoprotein E, is the primary genetic risk factor for late-onset Alzheimer's disease (AD). Apolipoprotein E ɛ4 allele (APOE4) carriers have alterations in brain structure and function (as measured by brain imaging) even as young adults. Examination of this population is valuable in further identifying details of these functional changes and their association with vulnerability to AD decades later.

Electrophysiological phenotypes of MeCP2 A140V mutant mouse model.

Aims: MeCP2 gene mutations are associated with Rett syndrome and X-linked mental retardation (XLMR), diseases characterized by abnormal brain development and function. Recently, we created a novel MeCP2 A140V mutation mouse model that exhibited abnormalities of cell packing density and dendritic branching consistent with that seen in Rett syndrome patients as well as other MeCP2 mutant mouse models. Therefore, we hypothesized that some deficits of neuronal and synaptic functions might also be present in the A140V mutant model.

Skewed allele-specific expression of the NF1 gene in normal subjects: a possible mechanism for phenotypic variability in neurofibromatosis type 1.

Neurofibromatosis type 1 is an autosomal dominant disorder characterized by neurocutaneous abnormalities, learning disabilities, and attention-deficit disorder. Neurofibromatosis type 1 symptom severity can be highly variable even within families where all affected members carry the same mutation. We hypothesized that variation in the expression of the normal NF1 allele may be a mechanism that participates in producing variable phenotypes.

Evidence for population variation in TSC1 and TSC2 gene expression.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder caused by mutations in one of two genes, TSC1 or TSC2, which encode the proteins hamartin and tuberin, respectively 123. Common features of TSC include intractable epilepsy, mental retardation, and autistic features. TSC is associated with specific brain lesions, including cortical tubers, subependymal nodules and subependymal giant cell astrocytomas.

Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation.

Background: Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy.

Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: scarification vaccination.

In this study, we evaluated the efficacy of vaccinia virus (VACV) containing mutations in the E3L virulence gene to protect mice against a lethal poxvirus challenge after vaccination by scarification. VACV strains with mutations in the E3L gene had significantly decreased pathogenicity, even in immune deficient mice, yet retained the ability to produce a potent Th1-dominated immune response in mice after vaccination by scarification, while protecting against challenge with wild type, pathogenic VACV. Initial experiments were done using the mouse-adapted, neurovirulent Western Reserve (WR) strain of vaccinia virus.

Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: intra-nasal vaccination.

Vaccinia virus (VACV) has been used as the vaccine to protect against smallpox, and recombinant VACVs have been used to develop vaccine candidates against numerous cancers and infectious diseases. Although relatively safe for use in humans, the strains of VACV that were used as smallpox vaccines led to several complications including, progressive infection in immune compromised individuals, eczema vaccination in individuals with a history of atopic dermatitis, and encephalitis and perimyocarditis in apparently healthy individuals. The work described in this paper focuses on attenuated strains of VACV that may have the potential for use as vaccine vectors with reduced pathogenicity.

Genetic aspects of neurocutaneous disorders.

Among the conditions that are included under the heading of "neurocutaneous disorders" are neurofibromatosis 1, tuberous sclerosis complex, von Hippel-Lindau, incontinentia pigmenti, Sturge-Weber syndrome, hypomelanosis of Ito, and linear nevus sebaceous syndromes. The clinical features, pathogenesis, and neurobiological basis of some of these disorders are discussed in other articles in this issue. We will focus on genetic aspects of a selected subgroup of these conditions, concentrating on the genetic defect, mutation spectrum, clinical genetic testing, and issues pertinent to counseling.

The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response.

Encephalitis is a rare, but serious complication from vaccination against smallpox using replication competent strains of vaccinia virus. In this report we describe mutants of vaccinia virus, containing N-terminal deletions of the vaccinia virus interferon resistance gene, E3L, that are attenuated for neuropathogenesis in a mouse model system. These recombinant viruses replicated to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice but failed to spread to the lungs or brain.