Transcriptomic profiling of Parkinson's disease brains reveals disease stage specific gene expression changes.

Parkinson´s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Aggravation of symptoms is mirrored by accumulation of protein aggregates mainly composed by alpha-synuclein in different brain regions, called Lewy bodies (LB). Previous studies have identified several molecular mechanisms as autophagy and inflammation playing a role in PD pathogenesis.

Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2, SFMBT2, AKAP6 and PHYHIP.

Enlargement of Geographic Atrophy From First Diagnosis to End of Life.

Importance: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking.

Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning.

Purpose: Current prediction models for advanced age-related macular degeneration (AMD) are based on a restrictive set of risk factors. The objective of this study was to develop a comprehensive prediction model applying a machine learning algorithm allowing selection of the most predictive risk factors automatically.

Design: Two population-based cohort studies.

Joint Contribution of Genetic Susceptibility and Modifiable Factors to the Progression of Age-Related Macular Degeneration over 10 Years: The Three Continent AMD Consortium Report.

Purpose: To assess joint effects of genetic and modifiable factors on the 10-year progression of age-related macular degeneration (AMD).

Design: Individual and pooled data analyses of 2 population-based cohorts.

Participants: Blue Mountains Eye Study (BMES) and Rotterdam Study (RS) participants (n = 835).

Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch's Membrane.

Purpose: Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited.

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future.

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

Purpose: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD).

Design: Meta-analysis.

Methods: setting: Three population-based cohorts.

Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations.

Objective: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk.

Design: Pooled data analysis of population-based cohorts.

Participants: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS).

Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium.

Purpose: Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies.

Design: Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC).

Pitfalls and practicalities in collecting and banking human brain tissues for research on psychiatric and neulogical disorders.

It is essential to examine brain materials for the understanding the cause and pathology of mental disorders. Recent methodological progress urges us to set up well qualified brain banks. Human tissue and Bio-banking is a complex field and the daily practice of brain banks needs to abide by several golden standards in order to avoid pitfalls in basic research: 1) A donor system in which informed consent is granted for the use of the samples for scientific research, including genetic analysis and access to medical records, 2) Rapid autopsy system, 3) Compatibility of protocols for procurement, management, handling and storage, 4) A generally accepted consensus on diagnostic criteria, 5) Quality control, 6) Abiding by local/international legal and ethical guidelines for work with human material, 7) Proper safety procedures.

The dynamic nature of Bruch's membrane.

Bruch's membrane (BM) is a unique pentalaminar structure, which is strategically located between the retinal pigment epithelium (RPE) and the fenestrated choroidal capillaries of the eye. BM is an elastin- and collagen-rich extracellular matrix that acts as a molecular sieve. BM partly regulates the reciprocal exchange of biomolecules, nutrients, oxygen, fluids and metabolic waste products between the retina and the general circulation.