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Article
Open AccessSingle-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these...
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Article
Open AccessDefective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration
Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of fr...
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Article
Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders
Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in...
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Article
Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Alzheimer’s disease (AD) is the most prevalent cause of dementia1. Although there is no effective treatment for AD, passive immunotherapy with monoclonal antibodies against amyloid beta (Aβ) is a promising therap...
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Article
Open AccessFunctional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease
Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson’s disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. Th...
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Article
Open AccessTREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for the clearance of myel...
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Article
Correction to: Overlap** genetic architecture between Parkinson disease and melanoma
The original version of this article unfortunately contained a mistake. Supplementary Tables 3 and 4 are not available with the rest of the supplementary material available online.
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Article
Overlap** genetic architecture between Parkinson disease and melanoma
Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these disease...
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Article
The TMEM106B FTLD-protective variant, rs1990621, is also associated with increased neuronal proportion
Apart from amyloid β deposition and tau neurofibrillary tangles, Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and astrocytosis in the cerebral cortex. The goal of thi...
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Article
Open AccessA single-nuclei RNA sequencing study of Mendelian and sporadic AD in the human brain
Alzheimer’s disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heter...
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Article
Open AccessTREM2 brain transcript-specific studies in AD and TREM2 mutation carriers
Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls. Similarly, TREM2 risk variant...
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Article
Open AccessParkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels
The genetic architecture of Parkinson’s Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the ex...
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Article
Open AccessPrimary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis
Mutations in the co- chaperone protein, CSPα, cause an autosomal dominant, adult-neuronal ceroid lipofuscinosis (AD-ANCL). The current understanding of CSPα function exclusively at the synapse fails to explain...
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Article
Open AccessResequencing analysis of five Mendelian genes and the top genes from genome-wide association studies in Parkinson’s Disease
Most sequencing studies in Parkinson’s disease (PD) have focused on either a particular gene, primarily in familial and early onset PD samples, or on screening single variants in sporadic PD cases. To date, th...
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Protocol
Pooled-DNA Sequencing for Elucidating New Genomic Risk Factors, Rare Variants Underlying Alzheimer’s Disease
Analyses of genome-wide association studies (GWAS) for complex disorders usually identify common variants with a relatively small effect size that only explain a small proportion of phenotypic heritability. Se...
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Article
Open AccessClinically early-stage CSPα mutation carrier exhibits remarkable terminal stage neuronal pathology with minimal evidence of synaptic loss
Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (AD-ANCL) is a multisystem disease caused by mutations in the DNAJC5 gene. DNAJC5 encodes Cysteine String Protein-alpha (CSPα), a putative synaptic pr...
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Article
Open AccessTREM2 is associated with increased risk for Alzheimer’s disease in African Americans
TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer’s disease (LOAD) in Caucasians of European and...
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Article
Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease
Whole-exome sequencing reveals that a rare variant of phospholipase D3 (PLD3(V232M)) segregates with Alzheimer’s disease status in two independent families and doubles risk for the disease in case–control series,...
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Article
Open AccessPooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer's disease Ibero-American cohort
Some familial Alzheimer's disease (AD) cases are caused by rare and highly-penetrant mutations in APP, PSEN1, and PSEN2. Mutations in GRN and MAPT, two genes associated with frontotemporal dementia (FTD), have be...
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Article
Exploration of genetic susceptibility factors for Parkinson’s disease in a South American sample
