Alzheimer's Disease Subtypes Proposed from Brain Gene Expression Profiles
|
By LabMedica International staff writers Posted on 18 Jan 2021 |
|
Image: Histopathology of neurofibrillary tangles in the brain of a patient with Alzheimer`s disease (Bielschowski silver stain) (Photo courtesy of Dimitri P. Agamanolis, MD).
Alzheimer’s disease (AD) is the most common form of dementia in the elderly, estimated to affect more than 5.8 million individuals in the USA and more than 50 million worldwide, with almost half of individuals aged over 75 years.
The neuropathological manifestations of AD traditionally include the accumulation of amyloid-beta (Aβ) peptide as extracellular plaques and hyperphosphorylated tau as intracellular neurofibrillary tangles (NFTs), typically identified on postmortem biopsy and used for definitive AD diagnosis.
A large team of scientists led by those at Icahn School of Medicine (New York, NY, USA) used transcriptome sequence data from more than 1,500 postmortem brain samples from individuals with or without AD to highlight several expression-based AD subtypes. They analyzed transcriptome data for more than 900 samples from the frontal pole (FP), superior temporal gyrus (STG), parahippocampal gyrus (PHG), and inferior frontal gyrus (IFG) brain regions in 364 Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB-AD) participants with or without AD or related dementia.
The scientists focused in on differential gene expression patterns in the PHG, adjusting for AD stage and severity. Their results pointed to five PHG expression-based subtypes of AD, falling into three main clusters, along with related molecular signatures, clinical features, and potential driver genes. The team identified three major molecular subtypes of AD corresponding to different combinations of multiple dysregulated pathways, such as susceptibility to tau-mediated neurodegeneration, amyloid-β neuroinflammation, synaptic signaling, immune activity, mitochondria organization, and myelination. Multiscale network analysis reveals subtype-specific drivers such as GABRB2, LRP10, MSN, PLP1, and ATP6V1A. The team reported their results were shored up with data for postmortem brain samples from another 615 AD cases or controls in Religious Orders Study–Memory and Aging Project (ROSMAP).
Bin Zhang, PhD, a Professor of Genetics and genomic Science and senior author of the study, said, “Understanding the genetic and molecular differences between molecular subtypes of AD within these data will provide novel insights into disease pathogenesis and offer new avenues for developing effective therapeutics.” The study was published on January 6, 2021 in the journal Science Advances.
Related Links:
Icahn School of Medicine
The neuropathological manifestations of AD traditionally include the accumulation of amyloid-beta (Aβ) peptide as extracellular plaques and hyperphosphorylated tau as intracellular neurofibrillary tangles (NFTs), typically identified on postmortem biopsy and used for definitive AD diagnosis.
A large team of scientists led by those at Icahn School of Medicine (New York, NY, USA) used transcriptome sequence data from more than 1,500 postmortem brain samples from individuals with or without AD to highlight several expression-based AD subtypes. They analyzed transcriptome data for more than 900 samples from the frontal pole (FP), superior temporal gyrus (STG), parahippocampal gyrus (PHG), and inferior frontal gyrus (IFG) brain regions in 364 Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB-AD) participants with or without AD or related dementia.
The scientists focused in on differential gene expression patterns in the PHG, adjusting for AD stage and severity. Their results pointed to five PHG expression-based subtypes of AD, falling into three main clusters, along with related molecular signatures, clinical features, and potential driver genes. The team identified three major molecular subtypes of AD corresponding to different combinations of multiple dysregulated pathways, such as susceptibility to tau-mediated neurodegeneration, amyloid-β neuroinflammation, synaptic signaling, immune activity, mitochondria organization, and myelination. Multiscale network analysis reveals subtype-specific drivers such as GABRB2, LRP10, MSN, PLP1, and ATP6V1A. The team reported their results were shored up with data for postmortem brain samples from another 615 AD cases or controls in Religious Orders Study–Memory and Aging Project (ROSMAP).
Bin Zhang, PhD, a Professor of Genetics and genomic Science and senior author of the study, said, “Understanding the genetic and molecular differences between molecular subtypes of AD within these data will provide novel insights into disease pathogenesis and offer new avenues for developing effective therapeutics.” The study was published on January 6, 2021 in the journal Science Advances.
Related Links:
Icahn School of Medicine
New
Gold Member
STI Test
Vivalytic MG, MH, UP/UU
New
Gold Member
Aspiration System
VACUSAFE
New
Electrolyte Analyzer
BKE-B
New
Automated Clinical Chemistry Analyzer
Envoy 500+
Latest Molecular Diagnostics News
- CE-Marked Blood Test Enables Monitoring of Neuroinflammation in Multiple Sclerosis
- Urine-Based Assay Predicts Severe Dengue Risk Early
- Ultrasensitive Assay Tracks Resistance Mutations MRD Monitoring
- FDA Clears At-Home HPV Test with Extended Genotyping for Cervical Screening
- Extracellular Vesicle RNA Biomarkers Enable Noninvasive IBD Diagnosis and Monitoring
- New Gene Signature Reveals Underdiagnosed Lung Cancer Subtype
- Genome Sequencing Identifies Noncoding Variants Causing Neonatal Diabetes
- Genetic Markers Predict GLP-1 Weight-Loss Response and Side Effects
- Noninvasive Urine Test Predicts Recurrence After BCG in Bladder Cancer
- Mesothelioma in Younger Adults Linked to Genetic Risk Factors
- Genetic Marker Predicts Early Heart Failure in Pulmonary Arterial Hypertension
- Immune Signatures in Blood Help Inform Cancer Risk in Lynch Syndrome
- Simple Blood Test Enables Multi-Disease Detection from Single Sample
- Rapid Point-of-Care RT-PCR Test Differentiates Influenza A/B and SARS-CoV-2 in Minutes
- Blood-Based ctDNA Test Enhances Risk Assessment in HPV-Related Throat Cancer
- WGS MCED Assay Demonstrates Rising Sensitivity and High Specificity
Channels
Clinical Chemistry
view channel
Study Finds ApoB Testing More Effective Than LDL for Guiding Lipid Therapy
Routine blood tests that measure low-density lipoprotein (LDL), commonly known as “bad” cholesterol, are widely used to guide lipid-lowering therapy, but they do not always provide a complete picture of... Read more
AI-Enabled POC Test Quantifies Multiple Cardiac Biomarkers
Cardiovascular diseases are a leading cause of death, responsible for nearly 20 million deaths each year. Timely triage of myocardial infarction and heart failure hinges on rapid cardiac biomarker measurement,... Read more
Next Generation Automated Analyzers Increase Throughput for Clinical Chemistry and Electrolyte Testing
Clinical laboratories continue to face staffing shortages, limited space, and growing test volumes that pressure chemistry and electrolyte workflows. Maintaining rapid turnaround times increasingly depends... Read more
Hematology
view channel
Routine Blood Test Parameters Link Anemia to Cancer Risk and Mortality
Anemia detected in routine care can signal underlying pathology and is frequently encountered in adults. Because it is defined by hemoglobin levels below the normal range, it is often evaluated with red... Read more
Prognostic Tool Guides Personalized Treatment in Rare Blood Cancer
Chronic myelomonocytic leukemia (CMML) is a rare blood cancer in which acquired genetic mutations in bone marrow stem cells drive disease. Stem cell transplantation is the only curative option but carries... Read more
Immunology
view channel
Study Finds Influenza Often Undiagnosed in Winter Deaths
Seasonal influenza drives substantial excess mortality, yet its contribution is often obscured when infections go undiagnosed near the time of death. Many deaths occur outside hospitals or in older adults... Read more
Combined Screening Approach Identifies Early Leprosy Cases
Leprosy remains a significant public health concern, with more than 200,000 new cases reported globally each year and early disease often escaping routine laboratory detection. In its initial phase, bacterial... Read more
Microbiology
view channel
RNA-Based Workflow Identifies Active Skin Microbes for Dermatology Research
Human skin carries diverse microbial communities that influence barrier function and inflammation, yet identifying which organisms are metabolically active has been challenging. DNA-based surveys catalog... Read more
Cost-Effective Sampling and Sequencing Workflow Identifies ICU Infection Hotspots
Intensive care units face persistent threats from hospital-acquired infections, increasingly driven by drug-resistant bacteria. Rapidly pinpointing environmental reservoirs and transmission hotspots remains... Read more
Pathology
view channel
AI Improves Completeness of Complex Cancer Pathology Reports
Oncology teams increasingly rely on pathology reports that integrate histopathology, immunohistochemistry, and rapidly expanding biomarker testing. As patients live longer and undergo repeated analyses... Read more
AI Tool Predicts Chemotherapy Response in Small Cell Lung Cancer
Small cell lung cancer often presents at an extensive stage and progresses rapidly, leaving little time to tailor first-line therapy. Clinicians currently lack biomarkers to guide which patients will benefit... Read more_image.png "Image: Through neoadjuvant therapy combining chemotherapy with immune checkpoint inhibitors (ICI) for 46 LAGC patients and single-cell transcriptome sequencing, researchers found that tumor cells in the treatment-sensitive group specifically upregulated MHC-II (tumor-specific major histocompatibility complex class II, tsMHC-II) molecules (photo courtesy of Science China Press)")
Tumor-Specific Biomarker Predicts Neoadjuvant Immunotherapy Response in Gastric Cancer
Gastric cancer is the fifth most common malignancy and the fourth leading cause of cancer mortality worldwide, with China bearing nearly half of the global burden. Only a subset of patients benefit from... Read more
Technology
view channel
Noninvasive Sputum Test Detects Early Lung Cancer
Early detection remains critical for improving outcomes in lung cancer, yet clinicians increasingly encounter indeterminate pulmonary nodules found incidentally or through screening, complicating decision-making.... Read more
New AI Tool Enables Rapid Treatment Selection in Pediatric Leukemia
Children with T-cell acute lymphoblastic leukemia face an aggressive disease that remains difficult to treat. Although remission rates have improved, many survivors experience long-term effects from intensive... Read more
Breakthrough Mass Spectrometry Design Could Enable Ultra-Low Abundance Detection
Mass spectrometry is central to identifying and quantifying molecules in complex biological samples, but conventional instruments typically analyze ions sequentially, which can limit detection of rare species.... Read more
Industry
view channel
Beckman Coulter Gains CE Mark for Rapid Assay Distinguishing Bacterial vs Viral Infections
Clinicians often struggle to distinguish bacterial from viral infections at first presentation because symptoms overlap and definitive culture or molecular results can take hours or days.... Read more
