Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects.

Hippocampal sclerosis dementia: An amnesic variant of frontotemporal degeneration.

Objective: To describe characteristics of hippocampal sclerosis dementia.

Methods: Convenience sample of Hippocampal sclerosis dementia (HSD) recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization.

Pharmacologic inhibition of ROCK2 suppresses amyloid-β production in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is the leading cause of dementia and has no cure. Genetic, cell biological, and biochemical studies suggest that reducing amyloid-β (Aβ) production may serve as a rational therapeutic avenue to delay or prevent AD progression. Inhibition of RhoA, a Rho GTPase family member, is proposed to curb Aβ production.

RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia.

The finding that a GGGGCC (G4C2) hexanucleotide repeat expansion in the chromosome 9 ORF 72 (C9ORF72) gene is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) links ALS/FTD to a large group of unstable microsatellite diseases. Previously, we showed that microsatellite expansion mutations can be bidirectionally transcribed and that these mutations express unexpected proteins by a unique mechanism, repeat-associated non-ATG (RAN) translation. In this study, we show that C9ORF72 antisense transcripts are elevated in the brains of C9ORF72 expansion-positive [C9(+)] patients, and antisense GGCCCC (G2C4) repeat-expansion RNAs accumulate in nuclear foci in brain.

Heat capacity singularity of binary liquid mixtures at the liquid-liquid critical point.

The critical anomaly of the isobaric molar heat capacity for the liquid-liquid phase transition in binary nonionic mixtures is explained through a theory based on the general assumption that their partition function can be exactly mapped into that of the Ising three-dimensional model. Under this approximation, it is found that the heat capacity singularity is directly linked to molar excess enthalpy. In order to check this prediction and complete the available data for such systems, isobaric molar heat capacity and molar excess enthalpy near the liquid-liquid critical point were experimentally determined for a large set of binary liquid mixtures.

Abnormal gephyrin immunoreactivity associated with Alzheimer disease pathologic changes.

Many neurodegenerative disorders involve the abnormal accumulation of proteins. In addition to the pathologic hallmarks of neurofibrillary tangles and β-amyloid plaques in Alzheimer disease (AD), here we show that abnormal accumulations of gephyrin, an inhibitory receptor-anchoring protein, are highly correlated with the neuropathologic diagnosis of AD in 17 AD versus 14 control cases. Furthermore, gephyrin accumulations were specific for AD and not seen in normal controls or other neurodegenerative diseases including Parkinson disease, corticobasal degeneration, and frontotemporal degeneration.

Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore Longitudinal Study of Aging.

Importance: Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear.

Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice.

Background: Though the precise cause(s) of Alzheimer's disease (AD) remain unknown, there is strong evidence that decreased clearance of β-amyloid (Aβ) from the brain can contribute to the disease. Therapeutic strategies to promote natural Aβ clearance mechanisms, such as the protein apolipoprotein-E (APOE), hold promise for the treatment of AD. The amount of APOE in the brain is regulated by nuclear receptors including retinoid X receptors (RXRs).

Beta-amyloid, phospho-tau and alpha-synuclein deposits similar to those in the brain are not identified in the eyes of Alzheimer's and Parkinson's disease patients.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders, and are characterized by deposition of specific proteins in the brain. If similar abnormal protein deposits are present in the eye, it would facilitate noninvasive diagnosis and monitoring of disease progression. We therefore evaluated expression of proteins associated with AD and PD pathology in postmortem eyes and brains in a case-control study.

Familial dementia with frontotemporal features associated with M146V presenilin-1 mutation.

Most of the mutations in the presenilin-1 gene (PS-1) are associated with familial Alzheimer's disease (AD). However, certain examples can be associated with frontotemporal dementia (FTD). We performed a clinical evaluation of individuals belonging to a family with the FTD phenotype, and additional molecular studies and neuropathological assessment of the proband.

Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: a case study at 11.7 T.

A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125-255 μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7 T.

Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease.

Huntington's disease (HD) is a devastating genetic neurodegenerative disease caused by CAG trinucleotide expansion in the exon-1 region of the huntingtin gene. Currently, no cure is available. It is becoming increasingly apparent that mutant Huntingtin (HTT) impairs metabolic homeostasis and causes transcriptional dysregulation.

A new genus and species of Leptocheliidae (Crustacea: Peracarida: Tanaidacea) from Isla del Coco (Costa Rica).

Samples from the scarcely-studied sedimentary seabed from the Isla del Coco (Costa Rica) yielded a single species of Tanaidacea, belonging to a new genus of Leptocheliidae, Cocotanais. The new genus shows affinities with Pseudonototanais and Heterotanais in bearing a conspicuous forcipate cheliped in the males, which in Cocotanais has a modified merus and carpal flange. Other distinct characters of the males are a triangular cephalothorax, a three-articled antennular peduncle and swollen bases of pereopods 4-6.

MicroRNA-205 regulates the expression of Parkinson's disease-related leucine-rich repeat kinase 2 protein.

Recent genome-wide association studies indicate that a simple alteration of Leucine-rich repeat kinase 2 (LRRK2) gene expression may contribute to the etiology of sporadic Parkinson's disease (PD). However, the expression and regulation of LRRK2 protein in the sporadic PD brains remain to be determined. Here, we found that the expression of LRRK2 protein was enhanced in the sporadic PD patients using the frontal cortex tissue from a set of 16 PD patients and 7 control samples.

Cerebral white matter disease is associated with Alzheimer pathology in a prospective cohort.

Background: Although magnetic resonance imaging (MRI)-detected white matter disease has been correlated with cognitive decline in the elderly individuals, it is unclear whether white matter disease is primarily responsible for the cognitive deterioration or whether another process is common to both white matter disease and dementia.

Methods: We examined the relationship between Alzheimer-type brain pathology at autopsy and MRI-detected cerebral white matter disease in 50 participants from the Baltimore Longitudinal Study of Aging Autopsy Program, a prospective study of aging that includes detailed cognitive assessments.

Results: White matter disease was quantitated in pre- and postmortem MRI scans using the Cardiovascular Health Study (CHS) criteria in a blinded manner.

Personality and resilience to Alzheimer's disease neuropathology: a prospective autopsy study.

Alzheimer's disease (AD) neuropathology is found at autopsy in approximately 30% of cognitively normal older individuals. We examined whether personality traits are associated with such resilience to clinical dementia in individuals with AD neuropathology. Broad factors and specific facets of personality were assessed up to 28 years (mean 11 ± 7 years) before onset of dementia and up to 30 years (mean 15 ± 7 years) before death in a cohort (n = 111) evaluated for AD neuropathology at autopsy.

Striatal neuronal loss correlates with clinical motor impairment in Huntington's disease.

Huntington's disease (HD) is characterized clinically by chorea, motor impairment, psychiatric manifestations, and dementia. Atrophy of the striatum is the neuropathological hallmark of HD, and previous studies have suggested that striatal atrophy correlates more closely with motor impairment than with chorea. Motor impairment, as measured by motor impairment score, correlates with functional disability in HD patients, but chorea does not.

Peripheral facial nerve lesions induce changes in the firing properties of primary motor cortex layer 5 pyramidal cells.

Facial nerve lesions elicit long-lasting changes in vibrissal primary motor cortex (M1) muscular representation in rodents. Reorganization of cortical representation has been attributed to potentiation of preexisting horizontal connections coming from neighboring muscle representation. However, changes in layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet been explored.

Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques.

The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The (11)C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in (11)C-PiB binding and the extent of agreement with neuropathological assessment have not been thoroughly investigated.

Longitudinal brain activity changes in asymptomatic Alzheimer disease.

Asymptomatic Alzheimer disease (ASYMAD) is characterized by normal cognition despite substantial AD pathology. To identify factors contributing to cognitive resilience, we compared early changes in regional cerebral blood flow (rCBF) in individuals subsequently diagnosed as ASYMAD with changes in cognitively impaired (CI) and normal older participants from the Baltimore Longitudinal Study of Aging. Participants underwent annual positron emission tomography (PET) rCBF measurements beginning 10.

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

Introduction: Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery.

Objective: Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury.

Materials And Methods: Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery.

Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases.

Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects.