Alpha-synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain.

Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders with alpha-synuclein (α-syn) aggregation pathology. Different strains of α-syn with unique properties are suggested to cause distinct clinical and pathological manifestations resulting in PD, MSA, or DLB. To study individual α-syn spreading patterns, we injected α-syn fibrils amplified from brain homogenates of two MSA patients and two PD patients into the brains of C57BI6/J mice.

LRP8 (rs5177) and CEP85L (rs11756438) are contributed to schizophrenia susceptibility in Iranian population.

Introduction Schizophrenia is recognized as one of the most important mental illnesses of the last century. Many genetic and environmental factors are involved in this condition. Recently, the genome-wide association study identified two significant genes LRP8 and CEP85L associated with psychiatric disorders.

Accelerated loss of hypoxia response in zebrafish with familial Alzheimer's disease-like mutation of presenilin 1.

Ageing is the major risk factor for Alzheimer's disease (AD), a condition involving brain hypoxia. The majority of early-onset familial AD (EOfAD) cases involve dominant mutations in the gene PSEN1. PSEN1 null mutations do not cause EOfAD.

Incomplete penetrance of gene for autosomal dominant form of cone-rod dystrophy.

: Cone-rod dystrophy (CRD) is an inherited retinal dystrophy that is transmitted via different modes of inheritance. Mutations in more than 30 genes have been identified to cause the disease. We aimed to investigate the genetic agents of two unrelated cone-rod dystrophy affected Iranian families with autosomal recessive inheritance patterns.

Impacts of Overweight and Obesity in Older Age on the Risk of Dementia: A Systematic Literature Review and a Meta-Analysis.

Background: It is unclear whether overweight and obesity in older age reduces or increases the risk of incident dementia.

Objective: To assess the impacts of overweight and obesity in older age on incident dementia.

Methods: We searched cohort studies reporting body weight measured in older age and dementia through PubMed, Embase, Medline, PyschInfo, and Cochrane library until July 2016.

Depressive symptoms as a barrier to engagement in physical activity in older adults with and without Alzheimer's disease.

Objectives: Physical activity shows promise for reduced risk of Alzheimer's disease (AD) and protection against cognitive decline among individuals with and without AD. Older adults face many barriers to adoption of physically active lifestyles and people with AD face even further challenges. Physical activity is a promising non-pharmacological approach to improve depressive symptoms, but little is known about the impact of depressive symptoms as a potential barrier to engagement in physical activity.

Dementia Primary Prevention Policies and Strategies and Their Local Implementation: A Scoping Review Using England as a Case Study.

Background: Understanding the policy context and how policy is implemented at the local and clinical level is an important precursor to developing preventive strategies focusing on dementia risk reduction in primary healthcare settings.

Objective: Using England as a case study, we review policies and strategies relevant to dementia prevention from the national to local level and how these are translated into primary healthcare services.

Methods: We conducted a scoping review covering: 1) identification of national, regional, and local policies and strategies that include dementia prevention; 2) identification of national guidelines for implementing dementia prevention at the clinical level; and 3) evaluation of the implementation of these at the clinical level.

Deletion of Alzheimer's Disease Risk Gene ABCA7 Alters White Adipose Tissue Development and Leptin Levels.

ATP-binding cassette A7 (ABCA7) is a genetic risk factor for late-onset Alzheimer's disease (AD). It belongs to a group of transporter genes that specializes in regulating lipid transport in the periphery as well as in the brain. ABCA7 has been implicated in a number of roles relating to AD pathology, including phagocytic clearance of amyloid-β peptides.

Practice guideline: Cervical and ocular vestibular evoked myogenic potential testing: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Objective: To systematically review the evidence and make recommendations with regard to diagnostic utility of cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP, respectively). Four questions were asked: Does cVEMP accurately identify superior canal dehiscence syndrome (SCDS)? Does oVEMP accurately identify SCDS? For suspected vestibular symptoms, does cVEMP/oVEMP accurately identify vestibular dysfunction related to the saccule/utricle? For vestibular symptoms, does cVEMP/oVEMP accurately and substantively aid diagnosis of any specific vestibular disorder besides SCDS?

Methods: The guideline panel identified and classified relevant published studies (January 1980-December 2016) according to the 2004 American Academy of Neurology process.

Results And Recommendations: Level C positive: Clinicians may use cVEMP stimulus threshold values to distinguish SCDS from controls (2 Class III studies) (sensitivity 86%-91%, specificity 90%-96%).

Parkinson's Disease Is Not Simply a Prion Disorder.

The notion that prion-like spreading of misfolded α-synuclein (α-SYN) causes Parkinson's disease (PD) has received a great deal of attention. Although attractive in its simplicity, the hypothesis is difficult to reconcile with postmortem analysis of human brains and connectome-mapping studies. An alternative hypothesis is that PD pathology is governed by regional or cell-autonomous factors.

Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy.

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective.

Accelerated aging exacerbates a pre-existing pathology in a tau transgenic mouse model.

Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back-crossed more than ten times onto a senescence-accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus.

Selective neuronal vulnerability in Parkinson disease.

Intracellular α-synuclein (α-syn)-rich protein aggregates called Lewy pathology (LP) and neuronal death are commonly found in the brains of patients with clinical Parkinson disease (cPD). It is widely believed that LP appears early in the disease and spreads in synaptically coupled brain networks, driving neuronal dysfunction and death. However, post-mortem analysis of human brains and connectome-mapping studies show that the pattern of LP in cPD is not consistent with this simple model, arguing that, if LP propagates in cPD, it must be gated by cell- or region-autonomous mechanisms.

Gene therapy for Parkinson's disease: Disease modification by GDNF family of ligands.

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain.

A novel multiplex assay for simultaneous quantification of total and S129 phosphorylated human alpha-synuclein.

Background: Alpha-synuclein (asyn) has been shown to play an important role in the neuropathology of Parkinson's disease (PD). In the diseased brain, classic intraneuronal inclusions called Lewy bodies contain abnormal formations of asyn protein which is mostly phosphorylated at serine 129 (pS129 asyn). This suggests that post-translational modifications may play a role in the pathogenic process.

FTD and ALS--translating mouse studies into clinical trials.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are related neurodegenerative disorders, which are characterized by a rapid decline in cognitive and motor functions, and short survival. Although the clinical and neuropathological characterization of these diseases has progressed--in part--through animal studies of pathogenetic mechanisms, the translation of findings from rodent models to clinical practice has generally not been successful. This article discusses the gap between preclinical animal studies in mice and clinical trials in patients with FTD or ALS.

Generation and characterization of novel conformation-specific monoclonal antibodies for α-synuclein pathology.

α-Synuclein (α-syn), a small protein that has the intrinsic propensity to aggregate, is implicated in several neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are collectively known as synucleinopathies. Genetic, pathological, biochemical, and animal modeling studies provided compelling evidence that α-syn aggregation plays a key role in the pathogenesis of PD and related synucleinopathies. It is therefore of utmost importance to develop reliable tools that can detect the aggregated forms of α-syn.

Symptoms of depression and rates of neurocognitive impairment in HIV positive patients in Beijing, China.

Background: In China an estimated 780,000 people are living with HIV (PLWH). In high-income countries PLWH are at increased risk of depression, with subsequent adverse consequences for quality of life, and HIV-related morbidity and mortality. There are few data from low-and middle-income countries.

Mapping the vestibular evoked myogenic potential (VEMP).

Effects of different electrode placements and indifferent electrodes were investigated for the vestibular evoked myogenic potential (VEMP) recorded from the sternocleidomastoid muscle (SCM). In 5 normal volunteers, the motor point of the left SCM was identified and an electrode placed there. A grid of 7 additional electrodes was laid out, along and across the SCM, based upon the location of the motor point.

Utility and limitations of Addenbrooke's Cognitive Examination-Revised for detecting mild cognitive impairment in Parkinson's disease.

Background/aims: To evaluate the utility of the Addenbrooke's Cognitive Examination-Revised (ACE-R) as a screening tool for mild cognitive impairment in Parkinson's disease (PD-MCI).

Methods: PD patients underwent comprehensive neuropsychological and neurological evaluations and ACE-R assessment.

Results: The ACE-R was superior to the Mini-Mental State Exam (MMSE) in detecting PD-MCI, with a cutoff score of ≤93 offering a sensitivity of 61% and a specificity of 64%.

Annual Research Review: Developmental considerations of gene by environment interactions.

Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large-scale longitudinal studies, ever-expanding knowledge of genetics, and increasing availability of neuroimaging data to provide endophenotypic bridges between molecules and behavior are beginning to provide some insight into interactions of developmental stage, genes, and the environment, although daunting challenges remain. Prominent amongst these challenges are difficulties in identifying and quantifying relevant environmental factors, discerning the relative contributions to multiply determined outcomes, and the likelihood that brain development is a non-linear dynamic process in which small initial differences may yield large later effects.