Longitudinal Cerebrospinal Fluid Biomarker Changes Predict Dementia
By LabMedica International staff writers Posted on 20 Jul 2015 |
Changes in key biomarkers of Alzheimer's disease (AD) during midlife as seen in brain scans and cerebrospinal fluid (CSF) of healthy adults may help identify those who will develop dementia years later.
The three CSF biomarker analytes that reflect and demonstrate excellent diagnostic and prognostic utility of the core neuropathologies in AD, are β-amyloid 42 (Aβ42), the primary constituent of amyloid plaques, total tau ,a marker of neuronal injury and/or death, and hyperphosphorylated tau (P-tau) which forms intraneuronal neurofibrillary tangles. Other recently identified biomarkers, include visinin-like protein 1 (VILIP-1) and chitinase-3-like protein 1 (YKL-40).
Scientists at Washington University School of Medicine (St. Louis, MO, USA) and their colleagues enrolled over a ten year period 169 cognitively normal participants ages 45 to 75 when they entered the study. DNA was extracted from peripheral blood samples and genotyping of Apolipoprotein E (APOE) was performed. A sample of CSF (20–30 mL) was collected by routine lumbar puncture at 8 AM after overnight fasting. Samples were processed into 500 μL aliquots and immediately frozen at -80 °C.
The CSF samples were analyzed for Aβ and tau proteins using single-analyte enzyme-linked immunosorbent assays (ELISAs). Samples were analyzed for Aβ1-40 (Aβ40), Aβ1-42 (Aβ42), total tau, and tau phosphorylated at threonine 181 (P-tau181) using the Improved INNOTEST ELISA (Fujirebio Europe; Gent, Belgium). In parallel, Aβ40, Aβ42, and total tau were measured at the same time from the same sample aliquot using a set of second-generation precision-based and accuracy-based EUROIMMUN ELISAs (EUROIMMUN; Luebeck, Germany).
The scientists found that drops in amyloid beta 42 levels in the cerebrospinal fluid among cognitively normal participants ages 45 to 54 are linked to the appearance of plaques in brain scans years later. They also found that tau and other biomarkers of brain-cell injury increase sharply in some individuals as they reach their mid-50s to mid-70s, and YKL-40 rises throughout the age groups focused on in the study. All of these changes were more pronounced in participants who carried a form of a gene that significantly increases the risk of Alzheimer's disease. The gene is known as APOE, and scientists have known that people with two copies of a particular version of this gene have up to 10 times the risk of developing Alzheimer's as those with other versions of the gene.
Anne Fagan, PhD, a professor of neurology and senior author said, “It's too early to use these biomarkers to definitively predict whether individual patients will develop Alzheimer's disease, but we're working toward that goal. One day, we hope to use such measures to identify and treat people years before memory loss and other cognitive problems become apparent. Alzheimer's is a long-term process, and that means we have to observe people for a long time to catch glimpses of it in action.” The study was published on July 6, 2015, in the journal JAMA Neurology.
Related Links:
Washington University School of Medicine
Fujirebio Europe
EUROIMMUN
The three CSF biomarker analytes that reflect and demonstrate excellent diagnostic and prognostic utility of the core neuropathologies in AD, are β-amyloid 42 (Aβ42), the primary constituent of amyloid plaques, total tau ,a marker of neuronal injury and/or death, and hyperphosphorylated tau (P-tau) which forms intraneuronal neurofibrillary tangles. Other recently identified biomarkers, include visinin-like protein 1 (VILIP-1) and chitinase-3-like protein 1 (YKL-40).
Scientists at Washington University School of Medicine (St. Louis, MO, USA) and their colleagues enrolled over a ten year period 169 cognitively normal participants ages 45 to 75 when they entered the study. DNA was extracted from peripheral blood samples and genotyping of Apolipoprotein E (APOE) was performed. A sample of CSF (20–30 mL) was collected by routine lumbar puncture at 8 AM after overnight fasting. Samples were processed into 500 μL aliquots and immediately frozen at -80 °C.
The CSF samples were analyzed for Aβ and tau proteins using single-analyte enzyme-linked immunosorbent assays (ELISAs). Samples were analyzed for Aβ1-40 (Aβ40), Aβ1-42 (Aβ42), total tau, and tau phosphorylated at threonine 181 (P-tau181) using the Improved INNOTEST ELISA (Fujirebio Europe; Gent, Belgium). In parallel, Aβ40, Aβ42, and total tau were measured at the same time from the same sample aliquot using a set of second-generation precision-based and accuracy-based EUROIMMUN ELISAs (EUROIMMUN; Luebeck, Germany).
The scientists found that drops in amyloid beta 42 levels in the cerebrospinal fluid among cognitively normal participants ages 45 to 54 are linked to the appearance of plaques in brain scans years later. They also found that tau and other biomarkers of brain-cell injury increase sharply in some individuals as they reach their mid-50s to mid-70s, and YKL-40 rises throughout the age groups focused on in the study. All of these changes were more pronounced in participants who carried a form of a gene that significantly increases the risk of Alzheimer's disease. The gene is known as APOE, and scientists have known that people with two copies of a particular version of this gene have up to 10 times the risk of developing Alzheimer's as those with other versions of the gene.
Anne Fagan, PhD, a professor of neurology and senior author said, “It's too early to use these biomarkers to definitively predict whether individual patients will develop Alzheimer's disease, but we're working toward that goal. One day, we hope to use such measures to identify and treat people years before memory loss and other cognitive problems become apparent. Alzheimer's is a long-term process, and that means we have to observe people for a long time to catch glimpses of it in action.” The study was published on July 6, 2015, in the journal JAMA Neurology.
Related Links:
Washington University School of Medicine
Fujirebio Europe
EUROIMMUN
Read the full article by registering today, it's FREE!
Register now for FREE to LabMedica.com and get complete access to news and events that shape the world of Clinical Laboratory Medicine.
- Free digital version edition of LabMedica International sent by email on regular basis
- Free print version of LabMedica International magazine (available only outside USA and Canada).
- Free and unlimited access to back issues of LabMedica International in digital format
- Free LabMedica International Newsletter sent every week containing the latest news
- Free breaking news sent via email
- Free access to Events Calendar
- Free access to LinkXpress new product services
- REGISTRATION IS FREE AND EASY!
Sign in: Registered website members
Sign in: Registered magazine subscribers
Latest Immunology News
- AI Predicts Tumor-Killing Cells with High Accuracy
- Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies
- AI Tool Precisely Matches Cancer Drugs to Patients Using Information from Each Tumor Cell
- Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment
- Testing Method Could Help More Patients Receive Right Cancer Treatment
- Groundbreaking Test Monitors Radiation Therapy Toxicity in Cancer Patients
- State-Of-The Art Techniques to Investigate Immune Response in Deadly Strep A Infections
- Novel Immunoassays Enable Early Diagnosis of Antiphospholipid Syndrome
- New Test Could Predict Immunotherapy Success for Broader Range Of Cancers
- Simple Blood Protein Tests Predict CAR T Outcomes for Lymphoma Patients
- Cell Sorter Chip Technology to Pave Way for Immune Profiling at POC
- Chip Monitors Cancer Cells in Blood Samples to Assess Treatment Effectiveness
- Automated Immunohematology Approaches Can Resolve Transplant Incompatibility
- AI Leverages Tumor Genetics to Predict Patient Response to Chemotherapy
- World’s First Portable, Non-Invasive WBC Monitoring Device to Eliminate Need for Blood Draw
- Predictive T-Cell Test Detects Immune Response to Viruses Even Before Antibodies Form