Publications by authors named "Laura B Cantwell"
Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored.
View Article and Find Full Text PDFIntroduction: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.
Methods: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites.
Article Synopsis
- - The study addresses the issue of limited ancestral diversity in genome-wide association studies (GWAS), which makes it hard to find genetic risk variants in non-European ancestry groups, focusing on Alzheimer's Disease (AD).
- - Researchers analyzed a multi-ancestry GWAS dataset within the Alzheimer's Disease Genetics Consortium (ADGC) involving individuals from various ancestries, identifying 13 shared risk loci and 3 ancestry-specific loci, highlighting the benefits of diverse samples.
- - The findings underscore the importance of including underrepresented populations in genetic research, suggesting that even smaller sample sizes can lead to the discovery of novel genetic variants related to AD and implicating specific biological pathways like amyloid regulation and neuronal development.
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.
View Article and Find Full Text PDFImportance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated.
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Article Synopsis
- Late-onset Alzheimer's disease (LOAD) is the most common type of dementia and is influenced by genetics.
- Researchers studied a lot of people (94,437) to find specific genes that may increase the risk of developing LOAD, confirming 20 known ones and discovering 5 new ones.
- They also found that certain genetic traits related to the immune system and how the brain processes proteins are linked to a higher risk of LOAD, suggesting there are more rare genes yet to be identified that could also play a role.
Article Synopsis
- * Our research uncovered three significant variants: a protective variant in the PLCG2 gene and risk variants in ABI3 and TREM2, known for their roles in Alzheimer's susceptibility.
- * The findings emphasize the importance of microglia, immune cells in the brain, suggesting that their genetic variations may contribute directly to the progression of Alzheimer's disease.
Importance: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays.
Objective: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals.
Introduction: African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g.
View Article and Find Full Text PDFCorticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.
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- - The study investigates a rare variant in the APP gene (A673T) that may protect against late-onset Alzheimer's disease (AD), originally found in Iceland, by comparing its frequency in US and Swedish populations.
- - Researchers conducted a case-control analysis involving over 17,000 participants (including AD cases and cognitively normal controls) from multiple medical centers to assess the prevalence of this variant using advanced genotyping techniques.
- - Results showed only a few individuals with the A673T variant; specifically, 3 heterozygous cases were found among US participants, indicating that this variant is not common in the studied populations and may not significantly impact AD risk assessment.
Article Synopsis
- The study investigates how known genetic risk factors for late-onset Alzheimer disease (LOAD) influence the age at which symptoms appear in affected individuals, particularly focusing on the APOE locus and other established risk loci.
- Researchers utilized data from the Alzheimer Disease Genetics Consortium, analyzing 9,162 patients over several years, to determine the cumulative effects of these genetic factors on age at onset (AAO) of LOAD.
- Results indicated that variants at the APOE locus are strongly associated with earlier onset of Alzheimer’s symptoms, with other loci like CR1, BIN1, and PICALM showing statistically significant effects as well, together explaining a portion of the AAO variation.
Article Synopsis
- This study aimed to find new genes linked to late-onset Alzheimer's disease by analyzing a large dataset from the International Genomics of Alzheimer's Project Consortium, which included over 25,000 Alzheimer's patients and around 48,000 controls.
- Researchers discovered new significant genetic loci on chromosomes 8 and 14, expanding the understanding of genetic susceptibility to Alzheimer's beyond previously known genes.
- The newly identified genes are involved in processes related to energy metabolism, protein degradation, and immune response, highlighting potential new targets for therapy in treating Alzheimer's disease.
Importance: Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment.
Objective: To identify genetic loci associated with late-onset Alzheimer disease in African Americans.
Article Synopsis
- - Recent studies have discovered 9 new genetic risk factors (loci) linked to late-onset Alzheimer’s disease (LOAD) and suggest investigating how these affect gene expression in the brain.
- - Researchers analyzed gene expression in the cerebellum and temporal cortex of around 400 deceased individuals, testing for associations between the identified risk variants and specific genes located nearby.
- - The study found that certain genetic variants significantly impacted the expression of key genes related to LOAD, indicating that these eSNPs may help explain the connection between genetic risk factors and Alzheimer’s disease.
Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports.
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- The Alzheimer Disease Genetics Consortium (ADGC) conducted a thorough genome-wide association study on late-onset Alzheimer's disease, featuring a three-stage design that included both discovery and replication phases.
- The study identified significant genetic associations with several genes, notably MS4A4A, CD2AP, EPHA1, and CD33, showing strong statistical significance across all stages.
- Additionally, the research confirmed previous associations with other genes like CR1, CLU, BIN1, and PICALM as being linked to Alzheimer's susceptibility, while finding no association with the gene EXOC3L2.
Background: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source.
View Article and Find Full Text PDFObjectives: To determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes.
Design: Association study of AD and CLU, PICALM, CR1, and APOE genotypes.
Setting: Academic research institutions in the United States, Canada, and Israel.
Background: A number of countries have estimated the prevalence of acute gastroenteritis by asking survey respondents to recall past episodes of diarrhea; however, the recall period used varies between studies. We conducted a survey to examine the effects of 7-day and 1-month recall periods on the estimated annual episodes of acute gastroenteritis. Further, we examine whether asking first about illness in the previous 7 days affects a person's response to a 1-month recall period.
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