Publications by authors named "Nadia Dehghani"
Primary age-related tauopathy (PART) and Alzheimer's disease (AD) share hippocampal phospho-tau (p-tau) pathology but differ in p-tau extent and amyloid presence. As a result, PART uniquely enables investigation of amyloid-independent p-tau mechanisms during brain aging. We conducted the first epigenome-wide association (EWAS) study of PART, which yielded 13 new and robust p-tau/methylation associations.
View Article and Find Full Text PDFPolypathology is a major driver of heterogeneity in clinical presentation and extent of neurodegeneration (N) in patients with Alzheimer Disease (AD). Beyond amyloid (A) and tau (T) pathologies, over half of patients with AD have concomitant pathology such as α-synuclein (S) in mixed AD with Lewy Body Disease (LBD). Patients with Mixed Etiology Dementia (MED) such as AD+LBD have faster progression and potentially differential responses to targeted treatments, though the diagnosis of AD+LBD can be challenging given overlapping clinical and imaging features.
View Article and Find Full Text PDFArticle Synopsis
- * The study analyzed individuals with extreme genetic risk for AD using a GWAS approach that is not limited to AD symptoms, identifying 246 significant genetic loci, with 229 of these previously unreported in AD research.
- * Findings reveal new potential genetic markers for AD, like IL34 and KANSL1, and emphasize significant genetic correlations with various health-related outcomes, contributing to understanding prodromal symptoms and comorbidities linked to AD.
Article Synopsis
- Hereditary cerebellar ataxia (HCA) is a group of neurodegenerative disorders that cause problems with movement, speech, and balance, and this study aimed to identify the genetic causes in 19 families presumed to have autosomal recessive inheritance.
- Researchers classified different clinical syndromes of HCA and found that the most common causal genes linked to spastic ataxia and other specific syndromes.
- The study also identified new genetic variants, highlighted the importance of distinguishing between autosomal recessive and dominant forms, and suggested that impaired cytoskeleton function and DNA repair might be involved in these disorders.
Background: Copy number variants (CNVs) include deletions or multiplications spanning genomic regions. These regions vary in size and may span genes known to play a role in human diseases. As examples, duplications and triplications of SNCA have been shown to cause forms of Parkinson's disease, while duplications of APP cause early onset Alzheimer's disease (AD).
View Article and Find Full Text PDFThe majority of genome-wide association studies have been conducted using samples with a broadly European genetic background. As a field, we acknowledge this limitation and the need to increase the diversity of populations studied. A major challenge when designing and conducting such studies is to assimilate large samples sizes so that we attain enough statistical power to detect variants associated with disease, particularly when trying to identify variants with low and rare minor allele frequencies.
View Article and Find Full Text PDFArticle Synopsis
- Recent genetic studies have revealed significant risk variants affecting dementia with Lewy bodies (DLB), showing that common variants explain a limited portion of its genetic basis.
- The estimated heritability of DLB is significantly higher than past studies suggested, at 59.9%, indicating more complex genetic factors at play.
- Genetic correlation analysis revealed DLB is positively associated with education levels, contrasting with the relationship found in Alzheimer's disease, suggesting the need for larger genome-wide association studies (GWAS) to uncover new genetic risk factors for DLB.