Publications by authors named "Christine M Hulette"
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.
Article Synopsis
- Primary open-angle glaucoma is more common and severe in people of African descent compared to those of European or Asian ancestry, yet they are often overlooked in genetic research on this condition.
- The study conducts a genome-wide association study (GWAS) involving nearly 10,000 participants from various countries to identify genetic links to the disease.
- Results suggest significant genetic variants associated with primary open-angle glaucoma, highlighting the need for more focused research on affected populations for better understanding and treatment options.
Article Synopsis
- An amendment to the original paper has been released.
- You can find the amendment through a link provided at the top of the paper.
- This update may contain important changes or additional information related to the original content.
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.
Fatal Granulomatous Amebic Encephalitis in a Heart Transplant Patient: Clinical, Radiographic, and Autopsy Findings.
J Neuropathol Exp Neurol
November 2018
Article Synopsis
- Granulomatous amebic encephalitis is a rare but often fatal infection of the central nervous system, primarily affecting individuals with weakened immune systems.
- A case study described a 69-year-old heart transplant recipient who experienced rapid neurological decline five months after surgery, ultimately leading to his death despite medical intervention.
- An autopsy revealed brain abscesses containing amebic organisms, highlighting the importance of considering amebic encephalitis in immunocompromised patients presenting with new brain lesions.
Article Synopsis
- The study investigates how changes in gene and protein expression contribute to the development of late-onset Alzheimer's disease.
- Researchers utilized a robust analysis pipeline, including predicting gene expression, analyzing relationships between transcripts and proteins, and validating findings across two significant brain sample sets.
- HSPA2, a specific protein, emerged as a key regulator linked to increased levels of amyloid-beta and tau proteins, highlighting its importance in late-onset Alzheimer's disease processes.
Article Synopsis
- A study investigated the genetic overlap between 25 brain disorders using data from over 1.2 million individuals, finding that psychiatric disorders share more genetic risk compared to neurological disorders, which seem more distinct.
- The research identified significant relationships between these disorders and various cognitive measures, suggesting shared underlying traits.
- Simulations were conducted to understand how factors like sample size and diagnosis accuracy influence genetic correlations, emphasizing the role of common genetic variations in the risk of brain disorders.
Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly.
Cold Spring Harb Mol Case Stud
September 2017
Hemimegalencephaly (HME) is a heterogeneous cortical malformation characterized by enlargement of one cerebral hemisphere. Somatic variants in mammalian target of rapamycin (mTOR) regulatory genes have been implicated in some HME cases; however, ∼70% have no identified genetic etiology. Here, we screened two HME patients to identify disease-causing somatic variants.
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- * 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.
Objective: Hippocampal sclerosis is the most common neuropathologic finding in cases of medically intractable mesial temporal lobe epilepsy. In this study, we analyzed the gene expression profiles of dentate granule cells of patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations, and to shed light on the transcriptional changes associated with hippocampal sclerosis.
Methods: RNA was extracted, and complementary DNA (cDNA) was prepared and amplified from dentate granule cells that had been harvested by laser capture microdissection from surgically resected hippocampi from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis.
Article Synopsis
- - 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
- - 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.
Article Synopsis
- Clinicopathologic correlation studies are essential for Alzheimer disease research, but they face biases that can affect their applicability and the validity of cognitive-status correlations.
- Many elderly people have non-AD brain lesions that can influence cognition, complicating the interpretation of studies on cognitive impairment.
- Research supports the link between specific Alzheimer-related changes (like Aβ plaques and neurofibrillary tangles) and cognitive decline, with the severity of impairment being more closely related to the amount of neurofibrillary tangles present.
In this paper the authors describe the rare disorder of diffuse leptomeningeal oligodendrogliomatosis in a patient with an oligodendroglioma of the cauda equina who died suddenly. Reviewing this uncommon pathological entity is important so that it can be recognized and treated appropriately. This young, otherwise healthy woman with initial symptoms of low-back pain had a mass lesion of the cauda equina.
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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.
SORL1 has been identified as a major contributor to late onset Alzheimer's disease (LOAD). We test whether genetic variability in the 5' of SORL1 gene modulates the risk to develop LOAD via regulation of SORL1-messenger ribonucleic acid (mRNA) expression and splicing. Two brain structures, differentially vulnerable to LOAD pathology, were examined in 144 brain samples from 92 neurologically normal individuals.
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- - Metabolomics studies the biochemical changes in the body, helping to identify disruptions in metabolic networks that could link to diseases.
- - This study used an advanced technique to analyze cerebrospinal fluid samples from Alzheimer's patients and controls, finding significant metabolic changes in neurotransmitter and oxidative stress pathways.
- - The findings suggest that deeper research into metabolomic profiles could help develop biomarkers for Alzheimer's disease, supporting earlier diagnosis and intervention.
Genetic variability at the 3' region of SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson's disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However, the mechanism through which the 3' region of SNCA gene modulates the risk to develop sporadic PD remained elusive.
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- Allopregnanolone, a neurosteroid, has protective effects on brain health and is linked to myelination and neurogenesis, but its dysregulation may contribute to Alzheimer's disease (AD) and other neurodegenerative conditions.
- Research shows that allopregnanolone levels are significantly lower in the temporal cortex of AD patients, particularly in relation to disease stage, compared to cognitively healthy controls.
- Additionally, individuals with the APOE4 allele, which is associated with a higher risk of AD, also show reduced levels of allopregnanolone, suggesting that these neurosteroids may have implications for AD treatment and understanding its biology.
Article Synopsis
- Frontotemporal lobar degeneration (FTLD) is a leading cause of early-onset dementia, with FTLD-TDP being the most common type linked to TDP-43 protein inclusions.
- Researchers conducted a genome-wide association study with 515 FTLD-TDP patients and identified significant genetic links on chromosome 7p21, particularly related to the TMEM106B gene.
- Variants in TMEM106B may increase the risk of developing FTLD-TDP, especially in those with GRN mutations, indicating a potential genetic mechanism for this form of dementia.*
Article Synopsis
- Alzheimer's disease is a serious neurodegenerative condition that causes memory loss and cognitive difficulties, ultimately leading to death.
- Recent studies have identified genetic factors like the APOE epsilon4 allele that contribute to the risk of developing Alzheimer's.
- In a new genome-wide scan involving 331 patients and 368 controls, no significant new genetic variations were found, but a potential duplication in the CHRNA7 gene may be worth further study.
Article Synopsis
- Genetic variability in the SNCA gene has been linked to the risk of developing sporadic Parkinson's disease (PD), with evidence showing that SNCA gene expression affects PD pathology.
- The study analyzed human brain samples from different areas affected by PD to see how certain genetic variants influenced SNCA-mRNA levels.
- Findings revealed that the protective Rep1-259 bp allele reduced SNCA-mRNA levels significantly compared to risk-associated alleles, highlighting the importance of genetic regulation in PD development.
We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared with brains of nondemented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: nondemented subjects without significant AD type pathology ("Normal"; n = 20), nondemented subjects with frequent senile plaques at autopsy ("Preclinical AD"; n = 20), and subjects with frontotemporal dementia ("FTD"; n = 10). The groups were matched for sex and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described.
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