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 heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. Using bulk RNA-seq from the parietal lobes and deconvolution methods, we previously reported that brains exhibiting different AD genetic architecture exhibit different cellular proportions. Here, we sou...
Background 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 carriers also exhibit differential CSF TREM2 levels. TREM2 has three different alternative transcripts, but most of the functional studies only model the longest transcript. No studies have analyzed TREM2 expression levels or alternative splicing in brains from AD and cogniti...
Last.Carlos Cruchaga(WashU: Washington University in St. Louis)H-Index: 51
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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 this study is to investigate genetic factors associated with the neuronal proportion in health and disease. To identify cell-autonomous genetic variants associated with neuronal proportion in cortical tissues, we inferred cellular population structure from bulk RNA-Seq derived from 1536 indivi...
Alzheimer Disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis specifically in the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. We previously reported different cellular proportions between brains exhibiting different AD genetic architecture, that we identified using bulk RNA-seq from homogenized parietal lobes and deconvolution met...
Last.Carlos Cruchaga(WashU: Washington University in St. Louis)H-Index: 51
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Background: In previous studies, we observed decreased neuronal and increased astrocyte proportions in AD cases in parietal brain cortex by using a deconvolution method for bulk RNA-seq. These findings suggested that genetic risk factors associated with AD etiology have a specific effect in the cellular composition of AD brains. The goal of this study is to investigate if there are genetic determinants for brain cell compositions. Methods: Using cell type composition inferred from transcriptome ...
Last.Oscar Harari(WashU: Washington University in St. Louis)H-Index: 14
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Purpose of the Review This review summarizes the current state of the art of polygenic risk scores (PRSs) in the assessment of risk for neurodegenerative diseases.