Article
Biochemistry & Molecular Biology
Guilherme Povala, Bruna Bellaver, Marco Antonio De Bastiani, Wagner S. Brum, Pamela C. L. Ferreira, Andrei Bieger, Tharick A. Pascoal, Andrea L. Benedet, Diogo O. Souza, Ricardo M. Araujo, Bruno Zatt, Pedro Rosa-Neto, Eduardo R. Zimmer
Summary: Soluble amyloid-beta isoforms can predict tau pathology and neurodegeneration in cognitively unimpaired individuals with a high AUC. Proteomics analysis identified a group of promising proteins for improving prediction of these pathological features.
CELL AND BIOSCIENCE
(2021)
Article
Clinical Neurology
Joseph Therriault, Stijn Servaes, Cecile Tissot, Nesrine Rahmouni, Nicholas J. Ashton, Andrea Lessa Benedet, Thomas K. Karikari, Arthur C. Macedo, Firoza Z. Lussier, Jenna Stevenson, Yi-Ting Wang, Jaime Fernandez-Arias, Alyssa Stevenson, Kely Quispialaya Socualaya, Arlette Haeger, Tahnia Nazneen, Etienne Aumont, Ali Hosseini, Soham Rej, Paolo Vitali, Gallen Triana-Baltzer, Hartmuth C. Kolb, Jean-Paul Soucy, Tharick A. Pascoal, Serge Gauthier, Henrik Zetterberg, Kaj Blennow, Pedro Rosa-Neto
Summary: This study evaluated the performance of plasma and cerebrospinal fluid (CSF) p-tau(181), p-tau(217), and p-tau(231) in Alzheimer's disease (AD) diagnosis and found that plasma p-tau(217) had diagnostic performance equivalent to CSF, suggesting that it may help reduce the need for invasive lumbar punctures without compromising accuracy in AD identification.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biochemistry & Molecular Biology
Ioanna Tsantzali, Fotini Boufidou, Eleni Sideri, Antonis Mavromatos, Myrto G. Papaioannou, Aikaterini Foska, Ioannis Tollos, Sotirios G. Paraskevas, Anastasios Bonakis, Konstantinos I. Voumvourakis, Georgios Tsivgoulis, Elisabeth Kapaki, George P. Paraskevas
Summary: Analysis of classical cerebrospinal fluid biomarkers, especially in the context of a diagnostic system like AT(N), can be a significant tool for diagnosing Alzheimer's disease accurately during a patient's lifetime. Despite atypical clinical presentations, the classical biomarker profile was consistent with Alzheimer's disease in four patients, demonstrating the potential usefulness of these biomarkers for identifying the biochemical fingerprints of the disease.
Article
Chemistry, Analytical
Hye Jin Kim, Heeju Ahn, Hongrae Kim, Dongsung Park, Jin San Lee, Byung Chul Lee, Jinsik Kim, Dae Sung Yoon, Kyo Seon Hwang
Summary: The correlation between A beta and tau levels in plasma and brain accumulation has led to increased interest in quantifying these biomarkers in plasma as an alternative method for diagnosing Alzheimer's disease. A biosensor utilizing IMEs, PS, and DEP force showed high sensitivity and accuracy in distinguishing between AD patients and normal controls in clinical plasma samples. This technology has great potential for improving the clinical diagnosis of AD.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Review
Biochemistry & Molecular Biology
Long Wang, Xindong Shui, Yuelin Diao, Duoting Chen, Ying Zhou, Tae Ho Lee
Summary: This review summarizes the role of microRNAs in Alzheimer's disease. MicroRNAs can directly regulate the expression of Alzheimer's disease-related proteins, regulate the alternative splicing of tau and amyloid precursor protein, and modulate inflammatory responses. Additionally, circulating microRNAs in the blood may serve as noninvasive biomarkers for diagnosing Alzheimer's disease. Furthermore, microRNA-based therapeutics are being investigated as potential options for Alzheimer's disease treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Kaitlin B. Casaletto, Emma Nichols, Vahan Aslanyan, Stephanie M. Simone, Jennifer S. Rabin, Renaud La Joie, Adam M. Brickman, Kristen Dams-O'Connor, Priya Palta, Raj G. Kumar, Kristen M. George, Claudia L. Satizabal, Julie Schneider, Judy Pa
Summary: Females with Alzheimer's disease are more susceptible than males, and microglial activation plays an important mediating role in females but not males. This finding is crucial for understanding the pathogenesis of Alzheimer's disease and providing precision health care.
Review
Pathology
Khushboo Govind Faldu, Jigna Samir Shah
Summary: It is widely recognized that AD-related pathological changes occur long before the onset of symptoms, providing opportunities for early detection and treatment modification. This publication reviews the existing biomarker profile and explores the development of new biomarkers from various biological samples for AD screening, diagnosis, prognosis, and treatment monitoring, including microRNA, proteomics, metabolomics, artificial intelligence, and machine learning.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2022)
Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Geriatrics & Gerontology
Yuting Zhang, Upamanyu Ghose, Noel J. Buckley, Sebastiaan Engelborghs, Kristel Sleegers, Giovanni B. Frisoni, Anders Wallin, Alberto Lleo, Julius Popp, Pablo Martinez-Lage, Cristina Legido-Quigley, Frederik Barkhof, Henrik Zetterberg, Pieter Jelle Visser, Lars Bertram, Simon Lovestone, Alejo J. Nevado-Holgado, Liu Shi
Summary: The aim of this study is to use deep learning neural networks (NNs) to identify plasma proteins that predict amyloid, tau, and neurodegeneration (AT[N]) pathologies in early Alzheimer's disease (AD). These plasma proteins could potentially serve as blood-based biomarkers for the diagnosis and prediction of AD.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Medical Laboratory Technology
Kaj Blennow, Erik Stomrud, Henrik Zetterberg, Niels Borlinghaus, Veronika Corradini, Ekaterina Manuilova, Laura Muller-Hubner, Frances-Catherine Quevenco, Sandra Rutz, Oskar Hansson
Summary: This study evaluated the analytical performance of second-generation Elecsys CSF Gen II immunoassays and adjusted existing cut-offs to evaluate their potential utility in clinical routine. The findings suggest that the Gen II immunoassays have potential utility in aiding the diagnosis of Alzheimer's disease.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Xue Chen, Suixin Deng, Wenchao Wang, Stefania Castiglione, Zilei Duan, Lei Luo, Francesca Cianci, Xiaoxue Zhang, Jianglei Xu, Hao Li, Jizong Zhao, Peter Muiruri Kamau, Zhiye Zhang, James Mwangi, Jiali Li, Yousheng Shu, Xintian Hu, Michele Mazzanti, Ren Lai
Summary: This study reveals that the antimicrobial peptide LL-37 promotes the membrane translocation and integration of CLIC1, leading to microglial hyperactivation and neuroinflammation in Alzheimer's disease. The findings suggest that LL-37 may act as an endogenous agonist of CLIC1, driving the progression of AD.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Giovanni Bellomo, Antonio Indaco, Davide Chiasserini, Emanuela Maderna, Federico Paolini Paoletti, Lorenzo Gaetani, Silvia Paciotti, Maya Petricciuolo, Fabrizio Tagliavini, Giorgio Giaccone, Lucilla Parnetti, Giuseppe Di Fede
Summary: Automated determination of CSF core AD biomarkers was used to compare large cohorts of patients with different neurological disorders. Unsupervised Gaussian mixture model clustering algorithm classified patients into six clusters based on their CSF biomarker profile, some showing typical AD-like profile and others non-AD profile. By considering the frequencies of clinically defined OND and AD subjects in clusters, cluster-based cut-off values for A beta 42/A beta 40, p-tau, and t-tau were subsequently computed.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Article
Biochemistry & Molecular Biology
Rhett J. Britton, James M. Hutchison, Charles R. Sanders
Summary: In Alzheimer's disease (AD) research, the proteins of interest are amyloid precursor protein (APP) and tau, which play crucial roles in the disease mechanism. The relationship between A beta and tau pathologies remains unclear, with studies suggesting that A beta may induce or enhance tau protein formation in neurofibrillary tangles.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Jacinta Murray, Gregory Meloni, Etty P. Cortes, Ariadna KimSilva, Michelle Jacobs, Alyssa Ramkissoon, John F. Crary, Susan Morgello
Summary: Microglia play a role in the pathogenesis of Alzheimer's Disease (AD) and are associated with cognitive function. HIV status can predict microgliosis in the cortex, while traditional risk factors of AD have a stronger predictive power in the Aβ plaque microenvironment.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Lei Yu, Patricia A. Boyle, Aliza P. Wingo, Jingyun Yang, Tianhao Wang, Aron S. Buchman, Thomas S. Wingo, Nicholas T. Seyfried, Allan Levey, Philip L. De Jager, Julie A. Schneider, David A. Bennett
Summary: The cortical proteins implicated in Alzheimer's dementia were found to be more associated with non-AD neurodegenerative and cerebrovascular conditions rather than AD pathology. Some proteins were found to be pleiotropic and associated with both neurodegenerative and cerebrovascular pathologies.
Article
Psychiatry
Aliza P. Wingo, Mengli Wang, Jiaqi Liu, Michael S. Breen, Hyun-Sik Yang, Beisha Tang, Julie A. Schneider, Nicholas T. Seyfried, James J. Lah, Allan Levey, David A. Bennett, Peng Jin, Philip L. De Jager, Thomas S. Wingo
Summary: This study identified miR-29a-3p and miR-132-3p as novel and independent contributors to cognitive trajectory in older adults. These microRNAs have a significant impact on cognitive performance and are not influenced by common neurodegenerative pathologies. Additionally, the findings provide a foundation for future studies to explore the mechanisms and interventions to enhance cognitive stability in advanced age.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Neurosciences
Antoine Hone-Blanchet, Anastasia Bohsali, Lisa C. Krishnamurthy, Salman S. Shahid, Qixiang Lin, Liping Zhao, Aditya S. Bisht, Samantha E. John, David Loring, Felicia Goldstein, Allan Levey, James Lah, Deqiang Qiu, Bruce Crosson
Summary: The study revealed an association between frontal GABA+ levels and neurological aging, with GABA+ levels being reduced in MCI patients. Additionally, N-acetylaspartate relative to myo-inositol (tNAA/mI) predicted cognition in MCI patients only and was not related to CSF biomarkers.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Geriatrics & Gerontology
Aron S. Buchman, Lei Yu, Hans-Ulrich Klein, Andrea R. Zammit, Shahram Oveisgharan, Francine Grodstein, Shinya Tasaki, Allan Levey, Nicholas T. Seyfried, David A. Bennett
Summary: This study identified cortical proteins that may provide motor resilience in older adults. Five proteins were associated with progressive parkinsonism, suggesting their potential as therapeutic targets for maintaining motor function despite untreatable brain pathologies.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Thomas S. Wingo, Ekaterina S. Gerasimov, Yue Liu, Duc M. Duong, Selina M. Vattathil, Adriana Lori, Jake Gockley, Michael S. Breen, Adam X. Maihofer, Caroline M. Nievergelt, Karestan C. Koenen, Daniel F. Levey, Joel Gelernter, Murray B. Stein, Kerry J. Ressler, David A. Bennett, Allan Levey, Nicholas T. Seyfried, Aliza P. Wingo
Summary: This study identified 11 genes that contribute to the pathogenesis of PTSD by regulating brain protein abundance. Seven of these genes were replicated in further studies and four also showed association with PTSD at the brain mRNA level. These findings provide promising targets for mechanistic and therapeutic studies for PTSD.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Sruti Rayaprolu, Sara Bitarafan, Juliet Santiago, Ranjita Betarbet, Sydney Sunna, Lihong Cheng, Hailian Xiao, Ruth S. Nelson, Prateek Kumar, Pritha Bagchi, Duc M. Duong, Annie M. Goettemoeller, Viktor Janos Olah, Matt Rowan, Allan Levey, Levi B. Wood, Nicholas T. Seyfried, Srikant Rangaraju
Summary: By using cell type-specific protein labeling, we can better study the proteomic differences between neurons and astrocytes, and identify potential factors related to neurological diseases.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Girija Goyal, Pranav Prabhala, Gautam Mahajan, Bruce Bausk, Tal Gilboa, Liangxia Xie, Yunhao Zhai, Roey Lazarovits, Adam Mansour, Min Sun Kim, Aditya Patil, Danielle Curran, Jaclyn M. Long, Sanjay Sharma, Abidemi Junaid, Limor Cohen, Thomas C. Ferrante, Oren Levy, Rachelle Prantil-Baun, David R. Walt, Donald E. Ingber
Summary: In this study, researchers successfully cultured human ectopic lymphoid follicles with similar characteristics to lymphoid follicles in a microfluidic chip. These follicles showed improved immune responses to vaccines and can serve as an alternative to non-human primates for preclinical evaluation.
Article
Clinical Neurology
Thomas S. Wingo, Ekaterina S. Gerasimov, Se Min Canon, James J. Lah, Allan Levey, Aliza P. Wingo
Summary: The study found that depression manifesting after age 50 is associated with a genetic predisposition to Alzheimer's disease (AD), suggesting that genetic predisposition may be a factor contributing to the pathogenesis of mid-life depression. Further study is needed to investigate whether there is a shared genetic basis between mid-life depression and AD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Richa Batra, Matthias Arnold, Maria A. Woerheide, Mariet Allen, Xue Wang, Colette Blach, Allan Levey, Nicholas T. Seyfried, Nilufer Ertekin-Taner, David A. Bennett, Gabi Kastenmuller, Rima F. Kaddurah-Daouk, Jan Krumsiek
Summary: This study provides a comprehensive investigation and description of AD-associated metabolic changes, laying the foundation for future mechanistic research.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Aliza P. Wingo, Selina M. Vattathil, Jiaqi Liu, Wen Fan, David J. Cutler, Allan Levey, Julie A. Schneider, David A. Bennett, Thomas S. Wingo
Summary: This study found that LDL-C is associated with various neuropathological manifestations of AD independent of APOE, suggesting that LDL-C may be a modifiable risk factor for AD.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Clinical Neurology
Sumit Verma, Kelsey Perry Bullet, Raj Razdan Bullet, J. Christina Howell Bullet, Alice L. Dawson, William T. Hu
Summary: Gene therapies have revolutionized the treatment of spinal muscular atrophy (SMA), and studying biomarker changes can help assess disease progression and clinical outcomes. This study explores the longitudinal profiles of neurodegenerative and inflammatory markers in SMA patients undergoing antisense oligonucleotide therapy. The results suggest that declines in neurofilament light chain (NfL) levels are initially observed but increase with further treatment and improved motor functions. Additionally, the study identifies IL-8 levels as a potential biomarker for baseline function and short-term treatment response in SMA, with lower levels correlating with better outcomes.
Article
Multidisciplinary Sciences
Caroline M. Watson, Eric B. Dammer, Lingyan Ping, Duc M. Duong, Erica Modeste, E. Kathleen Carter, Erik C. B. Johnson, Allan I. Levey, James J. Lah, Blaine R. Roberts, Nicholas T. Seyfried
Summary: Alzheimer's disease (AD) is the most common form of dementia, and CSF beta-amyloid, total Tau, and phosphorylated Tau (pTau) are sensitive and specific biomarkers for diagnosis. However, these biomarkers do not capture the complex changes in AD brain beyond amyloid and Tau pathologies. This study used SRM-MS with isotopically labeled standards to quantify CSF protein biomarkers, identifying proteins that could distinguish AD stages and cognitive impairment.
Review
Clinical Neurology
William T. T. Hu
Review
Clinical Neurology
William T. Hu, Ashima Nayyar, Milota Kaluzova
Summary: Clinical prediction of underlying pathologic substrates in Alzheimer's disease dementia and related dementia syndromes has limited accuracy. Etiologic biomarkers, including CSF levels of AD proteins and cerebral amyloid PET imaging, have improved disease-modifying clinical trials in AD, but their integration into medical practice has been slow. This review discusses the expectations and future applicability of AD/ADRD biomarkers, proposes study designs and performance thresholds, and emphasizes the importance of equity, access, and reliability in biomarker research.
Article
Clinical Neurology
Sumit Verma, Kelsey Perry Bullet, Raj Razdan Bullet, J. Christina Howell Bullet, Alice L. Dawson, William T. Hu
Summary: Gene therapies have significantly changed the prospects for spinal muscular atrophy (SMA) and provide a unique opportunity to study longitudinal biomarker changes in correlation with reduced disease burden and improved clinical outcomes. Recent findings suggest that declining levels of the neurodegenerative marker neurofilament light chain (NfL) in cerebrospinal fluid (CSF) correlate with clinical response in children receiving serial anti-sense oligonucleotide therapy. However, as more children undergo single-dose gene replacement therapy, CSF NfL levels are no longer a practical biomarker. In this study, CSF samples were collected from 13 SMA children undergoing anti-sense oligonucleotide therapy to characterize the longitudinal profiles of NfL, as well as inflammatory and neuronal proteins. The researchers found that NfL levels initially decreased after treatment initiation but then increased with further treatment and improved motor functions. They also identified IL-8 levels as a potential biomarker for baseline function and short-term treatment response in SMA.