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39 results on '"Auriel A. Willette"'

1. Biomarkers of Alzheimer syndrome and related dementias: A&D author's guide

Author

Michael W, Lutz, Ara S, Khachaturian, Henrik, Zetterberg, Kaj, Blennow, Auriel A, Willette, Michelle M, Mielke, Kathleen M, Hayden, Hiroko H, Dodge, Yi, Tang, Barry D, Greenberg, Walter A, Kukull, and Zaven S, Khachaturian

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Editorial, Developmental Neuroscience, Alzheimer Disease, Epidemiology, Health Policy, Humans, Dementia, Neurology (clinical), Geriatrics and Gerontology, Biomarkers
Published
2022

2. Impact of COVID‐19 on the Onset and Progression of Alzheimer's Disease and Related Dementias: A Roadmap for Future Research

Author

Marcia N. Gordon, Michael T. Heneka, Lydia M. Le Page, Christian Limberger, David Morgan, Andrea J. Tenner, Niccolò Terrando, Auriel A. Willette, and Sara A. Willette

Subjects
Aging, Epidemiology, Clinical Sciences, Neurodegenerative, Alzheimer's Disease, Cellular and Molecular Neuroscience, Developmental Neuroscience, Alzheimer Disease, Behavioral and Social Science, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Humans, Cognitive Dysfunction, Aetiology, delerium, systemic inflammation, caregiver burden, SARS-CoV-2, Prevention, Health Policy, Rehabilitation, longitudinal cohort, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), COVID-19, Brain Disorders, Psychiatry and Mental health, Infectious Diseases, Caregivers, Geriatrics, Neurological, Communicable Disease Control, Alzheimer's risk factor, Dementia, Mental health, Neurology (clinical), Geriatrics and Gerontology
Abstract

COVID-19 causes lasting neurological symptoms in some survivors. Like other infections, COVID-19 may increase risk of cognitive impairment. This perspective highlights four knowledge gaps about COVID-19 that need to be filled to avoid this possible health issue. The first is the need to identify the COVID-19 symptoms, genetic polymorphisms and treatment decisions associated with risk of cognitive impairment. The second is the absence of model systems in which to test hypotheses relating infection to cognition. The third is the need for consortia for studying both existing and new longitudinal cohorts in which to monitor long term consequences of COVID-19 infection. A final knowledge gap discussed is the impact of the isolation and lack of social services brought about by quarantine/lockdowns on people living with dementia and their caregivers. Research into these areas may lead to interventions that reduce the overall risk of cognitive decline for COVID-19 survivors.

Published
2021

3. Oxidative stress biomarkers and longitudinal changes in human brain imaging across the Alzheimer’s disease continuum

Author

Auriel A Willette, Tianqi Li, Sara A Willette, Brittany A Larsen, Amy Pollpeter, Brandon S Klinedinst, Shannin Moody, Neil Barnett, Mohammadiarvejeh Parvin, Colleen Pappas, Mochel Jonathan, Karin Allenspach‐Jorn, and Qian Wang

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2022

6. APOE , TOMM40 , and Sex Interactions on Neural Network Connectivity

Author

Tianqi Li, Colleen Pappas, Scott T Le, Qian Wang, Brandon S Klinedinst, Brittany A Larsen, Amy Pollpeter, Ling Yi Lee, Michael W Lutz, William Kirby Gottschalk, Russell H Swerdlow, Kwangsik Nho, and Auriel A Willette

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

7. Die Young as Late as Possible Project: Trajectory analysis of cognitive aging

Author

Hardeep K. Obhi, Colleen Pappas, Auriel A. Willette, Brandon S. Klinedinst, and Elizabeth A. Shirtcliff

Subjects
Cognitive aging, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Trajectory analysis, Neurology (clinical), Geriatrics and Gerontology, Psychology, Die (integrated circuit), Cognitive psychology
Published
2020

8. In preclinical AD, impaired amyloid clearance and mitochondrial function underlie associations between white matter integrity and glucose regulation deficits

Author

Scott T. Le, Brittany Larsen, Brandon S. Klinedinst, Auriel A. Willette, Qian Wang, Amy Pollpeter, and Colleen Pappas

Subjects
medicine.medical_specialty, Amyloid, Epidemiology, business.industry, Health Policy, White matter, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, medicine.anatomical_structure, Developmental Neuroscience, Internal medicine, medicine, Blood sugar regulation, Neurology (clinical), Geriatrics and Gerontology, business, Function (biology)
Published
2020

9. Sex and sex hormones largely explain associations between glucose levels and brain atrophy in AD‐sensitive regions

Author

Brandon S. Klinedinst, Auriel A. Willette, Qian Wang, Scott T. Le, Colleen Pappas, Amy Pollpeter, and Brittany Larsen

Subjects
medicine.medical_specialty, Epidemiology, Health Policy, Biology, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Atrophy, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, Hormone
Published
2020

11. Family history and TOMM40 '523 interactive associations with memory in middle‐aged and Alzheimer's disease cohorts

Author

Allen D. Roses, Auriel A. Willette, Sterling C. Johnson, Bruce P. Hermann, Alexandra M.V. Wennberg, Rebecca L. Koscik, Michael W. Lutz, N. Maritza Dowling, Joseph L. Webb, Jennifer M. Oh, Sanjay Asthana, and Barbara B. Bendlin

Subjects
0301 basic medicine, Gerontology, Epidemiology, Health Policy, Physiology, Cognition, Disease, Biology, medicine.disease, Outer mitochondrial membrane, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Developmental Neuroscience, Global function, medicine, Biomarker (medicine), Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, Family history, 030217 neurology & neurosurgery, Cohort study
Abstract

Introduction Family history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa ( TOMM40 ) rs10524523 (‘523) poly-T length on memory decline. Methods For 912 nonapolipoprotein e4 middle-aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 ‘523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal fluid mitochondrial function biomarker was also assessed. Results For FH negative participants, gene-dose preservation of memory and global cognition was seen for "very long" versus "short" carriers. For FH positive, an opposite gene-dose decline was seen for very long versus short carriers. Maternal FH was a stronger predictor in aged, but not middle-aged, participants. Similar gene-dose effects were seen for the mitochondrial biomarker aspartate aminotransferase. Discussion These results may clarify conflicting findings on TOMM40 poly-T length and AD-related decline.

Published
2017

12. P3‐621: THE EFFECT OF LYSOPHOSPHATIDYLCHOLINE ON GREY MATTER VOLUME IN THE CEREBELLUM

Author

Auriel A. Willette, Kelsey E. McLimans, and Ye-Lim Lim

Subjects
Cerebellum, Epidemiology, Chemistry, Health Policy, Anatomy, Grey matter, Psychiatry and Mental health, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Lysophosphatidylcholine, medicine.anatomical_structure, Developmental Neuroscience, Volume (thermodynamics), medicine, Neurology (clinical), Geriatrics and Gerontology
Published
2018

13. P1‐484: CHOLECYSTOKININ INCREASES GRAY MATTER AND GLUCOSE UPTAKE IN THE BRAIN, LEADING TO INCREASED COGNITIVE FUNCTION, BUT IS CORRELATED WITH AN ACCUMULATION OF TAU AND PTAU FORMATIONS

Author

Brandon S. Klinedinst, Kelsey E. McLimans, Alexandra K. Plagman, and Auriel A. Willette

Subjects
medicine.medical_specialty, Epidemiology, Chemistry, Health Policy, Glucose uptake, Cognition, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, Cholecystokinin
Published
2018

15. P4‐300: SERUM VITAMIN B12 AND 5‐METHYLTETRAHYDROFOLATE‐HOMOCYSTEINE METHYLTRANSFERASE REDUCTASE SNPS PREDICT GREY MATTER AND GLUCOSE METABOLISM ACROSS THE AD SPECTRUM

Author

Kelsey E. McLimans, Ana D. Collazo-Martinez, Auriel A. Willette, and Siobhan M. Hoscheidt

Subjects
medicine.medical_specialty, biology, Epidemiology, Chemistry, Health Policy, 5-Methyltetrahydrofolate, Single-nucleotide polymorphism, Reductase, Grey matter, Carbohydrate metabolism, Psychiatry and Mental health, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, biology.protein, Neurology (clinical), Methionine synthase, Geriatrics and Gerontology, Serum vitamin b12
Published
2018

17. P3-261: HYPERGLYCEMIA AND NEURAL NETWORK FUNCTIONAL CONNECTIVITY: PEAKS AND THEN TROUGHS IN MID- TO LATE LIFE FOR PRECLINICAL AD AND ACROSS THE AD SPECTRUM

Author

Auriel A. Willette, Scott T. Le, Brandon S. Klinedinst, Colleen Pappas, Kelsey E. McLimans, Tovah Wolf, Qian Wang, and Alexandra K. Plagman

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Artificial neural network, Epidemiology, Health Policy, Functional connectivity, Neurology (clinical), Geriatrics and Gerontology, Biology, Spectrum (topology), Neuroscience
Published
2019

18. P3-260: FASTING GLUCOSE AND WHITE MATTER INTEGRITY: BENEFICIAL FOLLOWED BY DETRIMENTAL ASSOCIATIONS OVER TIME IN PRECLINICAL AD AND ALONG THE AD SPECTRUM

Author

Alexandra K. Plagman, Brandon S. Klinedinst, Kelsey E. McLimans, Tovah Wolf, Colleen Pappas, Qian Wang, Scott T. Le, and Auriel A. Willette

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, White matter, Fasting glucose, Psychiatry and Mental health, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2019

20. [IC‐P‐066]: AD FAMILY HISTORY MODULATES EFFECTS OF TOMM40 ‘523’ POLY‐T ON MTL ATROPHY AND HYPOMETABOLISM IN PRECLINICAL AND AD COHORTS

Author

Barbara B. Bendlin, Maritza Dowling, Joseph L. Webb, Rebecca L. Koscik, Allen D. Roses, Michael W. Lutz, Jennifer M. Oh, Sanjay Asthana, Auriel A. Willette, Bruce P. Hermann, Sterling C. Johnson, and Alexandra M.V. Wennberg

Subjects
Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Atrophy, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, Family history, business
Published
2017

21. [O1–01–01]: NEUROINFLAMMATION, DEPRESSION AND ALZHEIMER's DISEASE: INSIGHTS FROM THE KYNURENINE PATHWAY

Author

Joseph L. Webb, Robert Dantzer, and Auriel A. Willette

Subjects
medicine.medical_specialty, Kynurenine pathway, Epidemiology, business.industry, Health Policy, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Psychiatry, Neuroscience, Depression (differential diagnoses), Neuroinflammation
Published
2017

22. [P3–237]: NEUROPEPTIDE YY PLASMA CONCENTRATIONS IN ALZHEIMER's DISEASE

Author

Joseph L. Webb, Auriel A. Willette, Anna Collazo-Martinez, and Kylee Stitz

Subjects
medicine.medical_specialty, Epidemiology, Chemistry, Health Policy, Neuropeptide, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, Plasma concentration, medicine, Neurology (clinical), Geriatrics and Gerontology
Published
2017

23. [P3–238]: PERIPHERAL VERSUS CENTRAL INDEX OF METABOLIC DYSFUNCTION AND ASSOCIATIONS WITH CLINICAL AND PATHOLOGICAL OUTCOMES IN ALZHEIMER's DISEASE

Author

Kelsey E. McLimans, Auriel A. Willette, and Joseph L. Webb

Subjects
Pathology, medicine.medical_specialty, Index (economics), Epidemiology, business.industry, Health Policy, Disease, Peripheral, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Pathological
Published
2017

24. P3-233: ASSOCIATIONS OF CSF SUPEROXIDE DISMUTASE 1 WITH COGNITIVE, NEURAL, AND CSF BIOMARKERS ACROSS THE ALZHEIMER'S DISEASE SPECTRUM

Author

Auriel A. Willette, Colleen Pappas, Scott T. Le, Brandon S. Klinedinst, Kelsey E. McLimans, Qian Wang, Vellareddy Anatharam, Tovah Wolf, Bridget E Clark, Alexandra K. Plagman, and Anumantha G. Kanthasamy

Subjects
biology, Epidemiology, business.industry, Health Policy, Disease spectrum, Cognition, Superoxide dismutase, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Immunology, Csf biomarkers, biology.protein, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2019

25. P1-271: CSF GLUCOSE TRACKS BRAAK STAGE TAU DEPOSITION

Author

Colleen Pappas, Brandon S. Klinedinst, Kelsey E. McLimans, Alexandra K. Plagman, Anumantha G. Kanthasamy, Vellareddy Anatharam, Auriel A. Willette, and Scott T. Le

Subjects
Pathology, medicine.medical_specialty, CSF glucose, Epidemiology, Chemistry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Stage (hydrology), Geriatrics and Gerontology, Deposition (chemistry)
Published
2019

26. P2-257: BIOTINIDASE AS A NOVEL BIOMARKER OF NEURAL CHANGES AND AD CSF BIOMARKERS ACROSS THE ALZHEIMER'S DISEASE SPECTRUM

Author

Colleen Pappas, Qian Wang, Brandon S. Klinedinst, Scott T. Le, Kelsey E. McLimans, Auriel A. Willette, Alexandra K. Plagman, Tovah Wolf, and Kathleen Crank

Subjects
Epidemiology, business.industry, Health Policy, Disease spectrum, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Immunology, Csf biomarkers, Biotinidase, Biomarker (medicine), Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2019

27. P2-441: MITOCHONDRIAL BIOENERGETICS AND ALZHEIMER'S DISEASE: PYRUVATE KINASE AND ASSOCIATIONS WITH NEURAL AND COGNITIVE OUTCOMES

Author

Brandon S. Klinedinst, Colleen Pappas, Vellareddy Anatharam, Scott T. Le, Baillie Frizell, Auriel A. Willette, Anumantha G. Kanthasamy, and Jonathan Cerna

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Bioenergetics, Epidemiology, Health Policy, Cognition, Neurology (clinical), Disease, Geriatrics and Gerontology, Biology, Neuroscience, Pyruvate kinase
Published
2019

28. IC‐P‐065: AD Family History in Non‐APOE4S Modulates The Effects of '523 TOMM40 on Neuropathology and Memory Decline

Author

Allen D. Roses, Alexandra M.V. Wennberg, Michael W. Lutz, Auriel A. Willette, Barbara B. Bendlin, Joseph L. Webb, and Sterling C. Johnson

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Neuropathology, Geriatrics and Gerontology, Family history, Psychology, Neuroscience
Published
2016

29. P3‐079: Alzheimer's Disease Family History Modifies Tomm40 Effects on Vascular Risk Factors and Neurovascular Pathology

Author

Auriel A. Willette, Joseph L. Webb, Michael W. Lutz, and Alexandra M.V. Wennberg

Subjects
Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Vascular risk, Neurovascular bundle, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Disease family history, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2016

30. P2‐350: Alzheimer's Disease Outcomes and Altered Glucose Metabolism Linked with CSF Biomarker Autotaxin

Author

Auriel A. Willette and Kelsey E. McLimans

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Disease outcome, Health Policy, Carbohydrate metabolism, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, Csf biomarkers, Medicine, Neurology (clinical), Geriatrics and Gerontology, Autotaxin, business
Published
2016

31. IC‐P‐110: Autotaxin as a CSF Biomarker for Central Dysmetabolism and Alzheimer’s Disease Outcomes

Author

Auriel A. Willette and Kelsey E. McLimans

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Epidemiology, business.industry, Disease outcome, Health Policy, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Developmental Neuroscience, Internal medicine, Csf biomarkers, Medicine, Neurology (clinical), Geriatrics and Gerontology, Autotaxin, business, 030217 neurology & neurosurgery
Published
2016

32. P1‐328: Insulin Resistance and Longitudinal Associations with Temporal Atrophy Across The Alzheimer's Disease Spectrum

Author

Jonathan Cerna, Brandon S. Klinedinst, Auriel A. Willette, and Joseph L. Webb

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease spectrum, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Atrophy, Insulin resistance, Endocrinology, Developmental Neuroscience, Internal medicine, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2016

33. IC‐P‐068: Family History Modulates TOMM40's Effect on Alzheimer's Disease Vascular Risk Factors and Neurodegeneration

Author

Joseph L. Webb, Alexandra M.V. Wennberg, Barbara B. Bendlin, Allen D. Roses, Michael W. Lutz, Auriel A. Willette, and Sterling C. Johnson

Subjects
Epidemiology, business.industry, Health Policy, Neurodegeneration, Disease, Vascular risk, medicine.disease, Bioinformatics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, Family history, business
Published
2016

34. P2‐075: Alzheimer's Disease Family History Modulates Effects of '523 TOMM40 on Memory Decline and Medial Temporal Pathology

Author

Sterling C. Johnson, Barbara B. Bendlin, Michael W. Lutz, Joseph L. Webb, Alexandra M.V. Wennberg, Auriel A. Willette, and Allen D. Roses

Subjects
Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Disease family history, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published
2016

35. O1‐08‐06: Biomarkers of brain insulin resistance and neuroimaging correlates in early Alzheimer's disease

Author

Edward J. Goetzl, Dimitrios Kapogiannis, Maja Mustapić, Roger J. Mullins, Erez Eitan, Auriel A. Willette, and Mark P. Mattson

Subjects
Epidemiology, business.industry, Health Policy, Disease, Bioinformatics, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Insulin resistance, Developmental Neuroscience, Neuroimaging, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2015

36. IC‐P‐130: INSULIN RESISTANCE PREDICTS GLUCOSE UPTAKE IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE

Author

Dimitrios Kapogiannis and Auriel A. Willette

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Glucose uptake, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Insulin resistance, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment
Published
2014

37. P2–171: Midlife insulin resistance is associated with hypometabolism on FDG‐PET

Author

Bruce P. Hermann, Sanjay Asthana, Auriel A. Willette, Barbara B. Bendlin, Sterling Johnson, Rebecca L. Koscik, Mark A. Sager, Brad T. Christian, Asenath LaRue, Jennifer M. Oh, Alex C. Birdsill, and Erin M. Jonaitis

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Insulin resistance, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2013

38. O3‐06‐06: Metabolic syndrome in middle‐aged adults is associated with brain perfusion deficits

Author

Andrew L. Alexander, Asenath LaRue, Alex C. Birdsill, Catherine L. Gallagher, Sterling C. Johnson, Auriel A. Willette, Jennifer M. Oh, Ozioma C. Okonkwo, Mark A. Sager, Howard A. Rowley, Michele L. Ries, Sanjay Asthana, Nancy J. Davenport, Barbara B. Bendlin, Guofan Xu, and Cynthia M. Carlsson

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Perfusion scanning, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Cardiology, Medicine, Neurology (clinical), Geriatrics and Gerontology, Metabolic syndrome, business
Published
2012

39. O2‐01‐07: Baseline cerebrospinal fluid markers in healthy middle‐aged adults predict brain health at three‐year follow‐up

Author

Barbara B. Bendlin, Kaj Blennow, Mark A. Sager, Michele L. Ries, Henrik Zetterberg, Andrew L. Alexander, Amy A. Hawley, Luigi Puglielli, Sterling C. Johnson, Sanjay Asthana, Aparna Sodhi, and Auriel A. Willette

Subjects
medicine.medical_specialty, Epidemiology, medicine.drug_class, ADAM10, Caspase 3, Brain damage, Monoclonal antibody, Cellular and Molecular Neuroscience, Cerebrospinal fluid, Developmental Neuroscience, Internal medicine, medicine, biology, business.industry, Health Policy, Neurodegeneration, medicine.disease, Psychiatry and Mental health, Endocrinology, biology.protein, Biomarker (medicine), Neurology (clinical), Geriatrics and Gerontology, Antibody, medicine.symptom, business
Abstract

reflect specific cleavage sites in proteins and, due to their smaller size, will pass the BBB. Importantly, these smaller protein fragments include more information than their intact counterparts, namely that the proteins are degraded by specific enzymes, a cardinal feature of the brain damage in AD. Methods: Tau was cleaved with BACE1, ADAM10 and caspase 3, and fragments were identified by Mass spectrometry. 10 different fragments of tau was selected for monoclonal antibody development, and one assay measuring tau degradation mediated by the protease ADAM10 using an ELISA assay (NB191) was developed. 33 paired CSF and serum samples from patients with severe ADwere investigated. Brains fromwild-type (wt) and Tg4510 transgenic mice known to develop some aspects of Alzheimer’s disease were extracted. Results: The NB191 antibody recognized the cleavage site generated by ADAM10 with an IC50 of 12.5ng/mL, but not an elongated sequence with one more amino acid (see figure). Technically robust and measurable levels of the tau neoepitope in human Alzheimer’s disease patient sera and CSF samples with averages of 21ng/ml and 2ng/ mL respectively were obtained. Finally, we compared the levels of NB191 in CSF to the levels in serum and found a correlation of R 1⁄4 0.45, borderline significant. Brain extracts from Tg4510 mice had 10-fold elevated levels of the tau neoepitope when compared to wildtype controls (p

Published
2011

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