Validation of the Russian Version of the Positive and Negative Syndrome Scale (PANSS-Ru) and Normative Data.

: The Positive and Negative Syndrome Scale (PANSS) is widely used to assess psychopathology. The Russian version (PANSSRu) has not been validated, and normative data for the Russian-speaking population currently do not exist. The aims of this study were to 1) complete linguistic validation for the PANSSRu, 2) perform psychometric validation of the Russian translation, and 3) present norms for the Russian and Belarusian population.

Evaluation of Cholinergic Deficiency in Preclinical Alzheimer's Disease Using Pupillometry.

Cortical cholinergic deficiency is prominent in Alzheimer's disease (AD), and published findings of diminished pupil flash response in AD suggest that this deficiency may extend to the visual cortical areas and anterior eye. Pupillometry is a low-cost, noninvasive technique that may be useful for monitoring cholinergic deficits which generally lead to memory and cognitive disorders. The aim of the study was to evaluate pupillometry for early detection of AD by comparing the pupil flash response (PFR) in AD ( = 14) and cognitively normal healthy control (HC, = 115) participants, with the HC group stratified according to high ( = 38) and low ( = 77) neocortical amyloid burden (NAB).

Modulation of Retinal Arteriolar Central Reflection by APOE Genotype.

Objective: This study investigated the retinal arteriolar central reflex (CR, the central reflection observed in photographs of retinal vessels), which may provide information about micro-vascular health in the retina and also the brain, due to the homology between these vascular networks. The study also describes a novel computer based semi-automated technique that accurately quantifies retinal arteriolar CR and vessel width, and calculates the CR to vessel width ratio (CRR) from digital retinal photographs.

Methods: Digital retinal photographs were collected from participants in the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL), including 25 participants diagnosed with Alzheimer's disease (AD) (age 72.

Plasma Phospholipid and Sphingolipid Alterations in Presenilin1 Mutation Carriers: A Pilot Study.

Background And Objective: Aberrant lipid metabolism has been implicated in sporadic Alzheimer's disease (AD). The current study investigated plasma phospholipid and sphingolipid profiles in individuals carrying PSEN1 mutations responsible for autosomal dominant AD (ADAD).

Methods: Study participants evaluated were from the Perth and Melbourne sites of the Dominantly Inherited Alzheimer Network (DIAN) study.

Metal chaperones prevent zinc-mediated cognitive decline.

Zinc transporter-3 (ZnT3) protein is responsible for loading zinc into presynaptic vesicles and consequently controls the availability of zinc at the glutamatergic synapse. ZnT3 has been shown to decline with age and in Alzheimer's disease (AD) and is crucially involved in learning and memory. In this study, we utilised whole animal behavioural analyses in the ZnT3 KO mouse line, together with electrophysiological analysis of long-term potentiation in brain slices from ZnT3 KO mice, to show that metal chaperones (clioquinol, 30 mg/kg/day for 6weeks) can prevent the age-dependent cognitive phenotype that characterises these animals.

Comparison of MR-less PiB SUVR quantification methods.

(11)C-Pittsburgh compound B (PiB) is a positron emission tomography (PET) tracer designed to bind to amyloid-β (Aβ) plaques, one of the hallmarks of Alzheimer's disease (AD). The potential of PiB as an early marker of AD led to the increasing use of PiB in clinical research studies and development of several F-18-labeled Aβ radiotracers. Automatic quantification of PiB images requires an accurate parcellation of the brain's gray matter (GM).

Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET.

Non-invasive imaging of tau pathology in the living brain would be useful for accurately diagnosing Alzheimer's disease, tracking disease progression, and evaluating the treatment efficacy of disease-specific therapeutics. In this study, we evaluated the clinical usefulness of a novel tau-imaging positron emission tomography tracer 18F-THK5105 in 16 human subjects including eight patients with Alzheimer's disease (three male and five females, 66-82 years) and eight healthy elderly controls (three male and five females, 63-76 years). All participants underwent neuropsychological examination and 3D magnetic resonance imaging, as well as both 18F-THK5105 and 11C-Pittsburgh compound B positron emission tomography scans.

Progress towards a consensus on biomarkers for Alzheimer's disease: a review of peripheral analytes.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly population and attempts to develop therapies have been unsuccessful because there is no means to target an effective therapeutic window. CNS biomarkers are insightful but impractical for high-throughput population-based screening. Therefore, a peripheral, blood-based biomarker for AD would significantly improve early diagnosis, potentially enable presymptomatic detection and facilitate effective targeting of disease-modifying treatments.

Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer's disease.

Background: A practical biomarker is required to facilitate the preclinical diagnosis of Alzheimer's disease (AD).

Methods: Plasma amyloid beta (Aβ)1-40, Aβ1-42, Aβn-40, and Aβn-42 peptides were measured at baseline and after 18 months in 771 participants from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging. Aβ peptide levels were compared with clinical pathology, neuroimaging and neuropsychological measurements.

Altered neuronal markers following treatment with mood stabilizer and antipsychotic drugs indicate an increased likelihood of neurotransmitter release.

Objective: Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effects of these drugs on neuronal markers previously reported to be altered in subjects with psychiatric disorders.

Methods: Male Sprauge-Dawley rats were treated with vehicle (ethanol), lithium (25.5 mg per day), haloperidol (0.

Quetiapine monotherapy in bipolar II depression: combined data from four large, randomized studies.

Background: Despite being present in up to 1% of the population, few controlled trials have examined the efficacy of treatments for bipolar II depression. Pooled data are presented from four placebo-controlled studies (BOLDER I [5077US/0049] and II [D1447C00135]; EMBOLDEN I [D1447C00001] and II [D1447C00134]) that evaluated the efficacy of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder.

Methods: All studies included an 8-week, double-blind treatment phase in which patients were randomly assigned to treatment with quetiapine 300 mg/day, quetiapine 600 mg/day, or placebo.

Mitoprotective effect of Centella asiatica against aluminum-induced neurotoxicity in rats: possible relevance to its anti-oxidant and anti-apoptosis mechanism.

Role of mitochondrial dysfunction and oxidative stress has been well documented in various cognitive-related disorders such as Alzheimer's disease. Aluminum is a neurotoxic metal that may be involved in the progression of neurodegenerative processes. The antioxidant and memory enhancing effects of Centella asiatica (CA) are well known in the last few decades.

Longitudinal analysis of serum copper and ceruloplasmin in Alzheimer's disease.

Background: Several studies have reported that peripheral levels of copper and ceruloplasmin (CP) can differentiate patients with Alzheimer's disease (AD) from non-AD cases. The aim of this study was to determine the diagnostic value of serum copper, CP, and non-CP copper levels in a large cohort of AD subjects.

Methods: Serum copper and CP concentrations were measured at baseline and at 18-months in participants from the Australian Imaging Biomarkers and Lifestyle Study of Ageing.

Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network.

The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort.

Metal dyshomeostasis and oxidative stress in Alzheimer's disease.

Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation.

Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders.

The growing body of evidence implicating tumor necrosis factor-α (TNFα) in the pathophysiology of psychiatric disorders led us to measure levels of that protein in the cortex of subjects with major depressive disorders (MDD). Having reported an increase (458%) in the levels of the transmembrane (tmTNFα), but not the soluble (sTNFα), form of the protein in Brodmann's area (BA) 46, but not 24, in people with the disorder, we decided to examine additional components of TNFα-related pathways in the same regions in people with MDD and extend our studies to the same cortical regions of people with schizophrenia (Sz) and bipolar disorders (BD). Using postmortem tissue, western blots and quantitative PCR, we have now shown there is a significant increase (305%) in tmTNFα in Brodmann's area 24, but not 46, from subjects with BD, and that levels of the protein were not altered in Sz.

Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease.

Progressive cerebral deposition of the amyloid β-protein (Aβ) in brain regions serving memory and cognition is an invariant and defining feature of Alzheimer disease. A highly similar but less robust process accompanies brain aging in many nondemented humans, lower primates, and some other mammals. The discovery of Aβ as the subunit of the amyloid fibrils in meningocerebral blood vessels and parenchymal plaques has led to innumerable studies of its biochemistry and potential cytotoxic properties.

Modulating metals as a therapeutic strategy for Alzheimer's disease.

In 1906, Alois Alzheimer first characterized the disease that bears his name. Despite intensive research, which has led to a better understanding of the pathology, there is no effective treatment for this disease. Of the drugs approved by the US FDA, none are disease modifying, only symptomatic.

The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease.

Parkinson's disease (PD) is a progressive, chronic disease characterized by dyskinesia, rigidity, instability, and tremors. The disease is defined by the presence of Lewy bodies, which primarily consist of aggregated α-synuclein protein, and is accompanied by the loss of monoaminergic neurons. Current therapeutic strategies only give symptomatic relief of motor impairment and do not address the underlying neurodegeneration.

Metal chaperones: a holistic approach to the treatment of Alzheimer's disease.

As evidence for the role of metal ion dysregulation in the pathogenesis of multiple CNS disorders grows, it has become important to more precisely identify and differentiate the biological effects of various pharmacological modulators of metal ion homeostasis. This is particularly evident in disorders such as Alzheimer's disease (AD), where the use of metal chaperones (that transport metals), as opposed to chelators (which exclude metals from biological interactions), may prove to be the first truly disease modifying approach for this condition. The purpose of this mini-review is to highlight the emerging notion that metal chaperones, such as PBT2 (Prana Biotechnology), modulate a variety of critical pathways affecting key aspects of the AD cascade to provide a more "holistic" approach to the treatment of this disease.

Selective activation of muscarinic acetylcholine receptors for the treatment of schizophrenia.

It is being increasingly recognised that the future of drug development will need to be based on a comprehensive understanding of disease pathophysiology. Thus this review focuses on a growing body of information suggesting that decreases in muscarinic receptors are involved in the pathophysiology of schizophrenia. This review will address evidence to support the hypothesis that drugs that can increase the activity of muscarinic receptors have the potential to have antipsychotic affects and improve cognitive deficits in subjects with the schizophrenia.

Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels.

The catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) are neurotransmitters and hormones that mediate stress responses in tissues and plasma. The expression of β-amyloid precursor protein (APP) is responsive to stress and is high in tissues rich in catecholamines. We recently reported that APP is a ferroxidase, subsuming, in neurons and other cells, the iron-export activity that ceruloplasmin mediates in glia.

PBT2 Reduces Toxicity in a C. elegans Model of polyQ Aggregation and Extends Lifespan, Reduces Striatal Atrophy and Improves Motor Performance in the R6/2 Mouse Model of Huntington's Disease.

Background: There is evidence that interaction with biologically important metals, particularly copper and iron, contributes to the pathological aggregation and toxicity of the mutant huntingtin protein in HD. PBT2 is a novel 8-hydroxyquinoline drug in clinical trials for AD and HD which restores metal homeostasis and has demonstrated neuroprotective and cognitive benefits in animal models of AD and in a Phase IIa clinical trial in AD patients.

Objectives: We assessed efficacy of PBT2 to improve function in nematode and mouse models of HD.

The role of metallobiology and amyloid-β peptides in Alzheimer's disease.

The biggest risk factor for Alzheimer's disease is the process of ageing, but the mechanisms that lead to the manifestation of the disease remain to be elucidated. Why age triggers the disease is unclear but an emerging theme is the inability for a cell to efficiently maintain many key processes such as energy production, repair, and regenerative mechanisms. Metal ions are essential to the metabolic function of every cell.

Elevated labile Cu is associated with oxidative pathology in Alzheimer disease.

Oxidative stress is implicated in Alzheimer disease (AD) pathogenesis, for which evidence indicates that radical species are generated by the redox-active biometal Cu. The contribution of labile Cu to the oxidative stress observed in AD has not been evaluated. The Cu content of postmortem cortical tissue from nondemented elderly controls and AD cases was measured using inductively coupled plasma mass spectroscopy, and the proportion of labile Cu was assessed using the Cu-phenanthroline assay.