Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families

Background: Many families with clinical early-onset Alzheimer’s disease (EOAD) remain genetically unexplained. A combination of genetic factors is not standardly investigated. In addition to monogenic causes, we evaluated the possible polygenic architecture in a large series of families, to assess if genetic testing of familial EOAD could be...

Resilience and resistance to the accumulation of amyloid plaques and neurofibrillary tangles in centenarians: An age-continuous perspective

Introduction: With increasing age, neuropathological substrates associated with Alzheimer's disease (AD) accumulate in brains of cognitively healthy individuals—are they resilient, or resistant to AD-associated neuropathologies?. Methods: In 85 centenarian brains, we correlated NIA (amyloid) stages, Braak (neurofibrillary tangle) stages, and...

Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies

Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. Objective: We tested if genetic variants in part explain the heterogeneity in DLB. Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and...

The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity

Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-nucleotide-polymorphisms (SNPs) in...

SORL1 deficiency in human excitatory neurons causes APP-dependent defects in the endolysosome-autophagy network

Dysfunction of the endolysosomal-autophagy network is emerging as an important pathogenic process in Alzheimer's disease. Mutations in the sorting receptor-encoding gene SORL1 cause autosomal-dominant Alzheimer's disease, and SORL1 variants increase risk for late-onset AD. To understand the contribution of SORL1 mutations to AD pathogenesis,...

Immune response and endocytosis pathways are associated with the resilience against Alzheimer’s disease

Developing Alzheimer’s disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what...

Disruption of Functional Brain Networks in Alzheimer’s Disease: What Can We Learn from Graph Spectral Analysis of Resting-State Magnetoencephalography?

In Alzheimer’s disease (AD), structural and functional brain network organization is disturbed. However, many of the present network analysis measures require a priori assumptions and methodological choices that influence outcomes and interpretations. Graph spectral analysis (GSA) is a more direct algebraic method that describes network...

Key issues in successfull tranformations of industral heritage

Much of our industrial heritage lost its function in the transition from an industrial to a more service-based economy. Meantime, changing consumer preferences have shortened the functional and economic life cycle of buildings to such an extent that many have become vacant and obsolete. Developers tend to prefer to demolish such buildings and...

Sleutelfactoren in succesvol transformeren van verouderde industriele gebouwen

Transformeren en herbestemmen van industrieel vastgoed is niet zonder risico’s.<br/>Er kunnen zich allerlei organisatorische, financiële, procedurele en technische obstakels voordoen. Niettemin zijn verschillende gebouwen met succes getransformeerd tot nieuwe functies. Andere projecten zijn in voorbereiding. Dit artikel laat zien dat het denken...