Sarah Ahmed
A5034702104- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Lysosomal Storage Disorders Research
- Genomics and Rare Diseases
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Genetic Associations and Epidemiology
- Hemoglobinopathies and Related Disorders
- Alzheimer's disease research and treatments
- Neurological disorders and treatments
- Hereditary Neurological Disorders
- Telomeres, Telomerase, and Senescence
- Nonmelanoma Skin Cancer Studies
- Muscle Physiology and Disorders
- Connective tissue disorders research
- Child and Adolescent Psychosocial and Emotional Development
- Sphingolipid Metabolism and Signaling
- Stress Responses and Cortisol
- Iron Metabolism and Disorders
- Cancer-related gene regulation
- Fibromyalgia and Chronic Fatigue Syndrome Research
National Institute of Neurological Disorders and Stroke
2018-2023
St. Luke's University Health Network
2023
University Health System
2023
National Institutes of Health
2018-2021
University Hospital Mútua de Terrassa
2019
National Institute on Aging
2018-2019
University of Massachusetts Boston
2018
Newcastle University
2014
Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute the risk of disease, and currently 90 independent variants identified by genome-wide association studies. Thus far, number (including SNCA, LRRK2, GBA) contain variability across spectrum frequency effect, from rare, highly penetrant common alleles with small effect sizes. Variants in GBA, encoding enzyme glucocerebrosidase, are associated Lewy body diseases such as dementia. These variants,...
Massive genetic analysis identifies critical pathways and cell types involved in pathogenesis of amyotrophic lateral sclerosis.
<h3>Importance</h3> Pathogenic variants in<i>LRRK2</i>are a relatively common genetic cause of Parkinson disease (PD). Currently, the molecular mechanism underlying is unknown, and gain loss function (LOF) models pathogenesis have been postulated.<i>LRRK2</i>variants are reported to result in enhanced phosphorylation substrates increased cell death. However, double knockout of<i>Lrrk2</i>and its homologue<i>Lrrk1</i>results neurodegeneration mouse model, suggesting that may occur by LOF....
The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture neurodegenerative diseases.
Patients with corticobasal syndrome (CBS) present heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a analysis microtubule-associated protein tau (MAPT).We performed evaluation MAPT mutations in 826 neurologically healthy controls 173 cases CBS using Illumina NeuroChip genotyping array.We identified 2 patients heterozygous for mutation (p.V363I) that is...
Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson's Disease (PD). However, response to DBS varies, therefore, the ability predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations been reported among factors that influence DBS. disease accounts only minority of PD. The polygenic risk score (PRS) an indication cumulative genetic disease. PRS in PD has also correlated age onset and symptom...
Abstract Up to 80% of Parkinson's disease patients develop dementia, but time dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents clinical features similar Parkinson’s cognitive impairment precedes or coincides It remains controversial whether and are distinct conditions represent part a spectrum. The biological mechanisms underlying heterogeneity, in particular the development remain poorly understood, will likely be key understanding pathways and,...
Abstract The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts LBD cases and neurologically healthy controls to study the architecture this understudied form generate a resource for scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations gene GBA . Genetic scores demonstrate that shares profiles pathways with...
Abstract Squamoid eccrine ductal carcinoma (SEDC) is a poorly documented but likely underrecognized sweat gland malignancy with significant risk for local recurrence and potential metastasis rare disease-related mortality. Histopathologically, the tumor demonstrates biphasic differentiation pattern: superficially, has squamous [indistinguishable from well-differentiated cutaneous cell (cSCC)], while deeper aspect more infiltrative pattern prominent differentiation. Diagnosis of SEDC relies...
To examine the role of repeat expansions in pathogenesis frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), we performed sizing ten genetic loci previously implicated neurodegenerative diseases. We examined whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body (LBD) 3,158 neurologically healthy subjects. Pathogenic (range: 40 to 64 CAG repeats) huntingtin (HTT) gene were found three (0.12%) patients diagnosed with pure syndromes but not present LBD or...
ABSTRACT Background The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture neurodegenerative diseases. Objectives To perform largest Parkinson disease (PD) genome-wide association study (GWAS) restricted to a single country. Methods We performed GWAS both risk PD age-at-onset (AAO) in 7,849 Spanish individuals. Further analyses included population-specific haplotype...
Abstract Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of childhood motor disorder with heterogeneous clinical presentation. The underlying causes this condition are poorly understood, hindering the development effective therapies. In whole-exome sequencing trio-family study three unrelated juvenile patients diagnosed ALS and failure to thrive, we identified de-novo mutations in SPTLC1 (p.Ala20Ser two p.Ser331Tyr) not present their healthy parents or siblings. encodes subunit...
ABSTRACT Despite the considerable progress in unraveling genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand molecular mechanisms underlying disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify biological pathways and cell types involved ALS. This data-driven identified multiple aspects biology disease that resolved into broader themes, namely neuron projection morphogenesis, membrane trafficking ,...
Abstract Parkinson’s disease (PD) is a genetically complex disorder. Multiple genes have been shown to contribute the risk of PD, and currently 90 independent variants identified by genome-wide association studies. Thus far, number (including SNCA , LRRK2 GBA ) contain variability across spectrum frequency effect, from rare, highly penetrant common alleles with small effect sizes. Variants in encoding enzyme glucocerebrosidase, are associated Lewy body diseases such as PD dementia (LBD)....
SPTLC1 encodes a critical subunit of serine palmitoyltransferase, the enzyme catalyzing first and rate-limiting step in de novo sphingolipid biosynthesis, mutations this gene are known to cause hereditary sensory autonomic neuropathy, type 1A. Using exome sequencing, we identified coding variant an individual diagnosed with juvenile-onset amyotrophic lateral sclerosis (ALS), confirmed its pathogenicity by showing elevated plasma levels neurotoxic deoxymethyl-sphinganine. We also found 0.34%...