Article
Clinical Neurology
Clifford R. Jack Jr, Heather J. Wiste, Alicia Algeciras-Schimnich, Dan J. Figdore, Christopher G. Schwarz, Val J. Lowe, Vijay K. Ramanan, Prashanthi Vemuri, Michelle M. Mielke, David S. Knopman, Jonathan Graff-Radford, Bradley F. Boeve, Kejal Kantarci, Petrice M. Cogswell, Matthew L. Senjem, Jeffrey L. Gunter, Terry M. Therneau, Ronald C. Petersen
Summary: Staging the severity of Alzheimer's disease pathology is important for therapeutic trials and clinical prognosis. Biomarkers such as amyloid and tau PET can be used for disease staging, but plasma biomarkers would be more practical.
Article
Biochemistry & Molecular Biology
Chiara Giuseppina Bonomi, Agostino Chiaravalloti, Riccardo Camedda, Francesco Ricci, Nicola Biagio Mercuri, Orazio Schillaci, Giacomo Koch, Alessandro Martorana, Caterina Motta
Summary: The study investigates the association between markers of microglial and astrocytic activity and glucose uptake in patients with Alzheimer's Disease. The results suggest that there is a correlation between markers of astrogliosis and cortical glucose uptake in symptomatic sporadic AD, indicating the role of astrocytes in shaping regional hypometabolism and clinical presentation.
Review
Biochemistry & Molecular Biology
Giulia Bivona, Matilda Iemmolo, Giulio Ghersi
Summary: Despite the long history of Alzheimer's Disease, many aspects of the disease, including its pathogenesis, clinical spectrum definition, and therapeutic approach, remain obscure. The commonly used biomarkers, A beta and phosphorylated Tau protein aggregates, have their limitations and biases. The definition of Mild Cognitive Impairment, which is often used for AD prediction, has changed over time, leading to biases in related studies. Plasma biomarkers and novel candidate molecules, such as microglia biomarkers, show promise for diagnosing and monitoring AD. New AD markers are urgently needed for identifying molecular targets for treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Monica Diaz-Roman, Matias M. Pulopulos, Miguel Baquero, Alicia Salvador, Ana Cuevas, Ines Ferrer, Oana Ciopat, Enriqueta Gomez
Summary: Previous studies have shown a link between sleep-breathing disorders, especially obstructive sleep apnea (OSA), and an increased risk of progression to Alzheimer's disease (AD), as well as an association with cerebrospinal fluid (CSF) AD-biomarkers in patients with mild cognitive impairment (MCI). The study found that higher OSA severity was correlated with higher levels of P-tau and T-tau in CSF in MCI patients, even after adjusting for potential confounders.
Article
Clinical Neurology
Nuria Guillen, Jose Contador, Mariateresa Buongiorno, Ignacio Alvarez, Natalia Culell, Daniel Alcolea, Alberto Lleo, Juan Fortea, Gerard Pinol-Ripoll, Anna Carnes-Vendrell, Maria Lourdes Ispierto, Dolores Vilas, Albert Puig-Pijoan, Aida Fernandez-Lebrero, Mircea Balasa, Raquel Sanchez-Valle, Albert Llado
Summary: This study analyzed the agreement between AD CSF biomarkers and amyloid-PET, and found that there was incomplete agreement between single CSF biomarkers and amyloid-PET. However, biomarker ratios and combined biomarkers improved the agreement.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Erica S. Modeste, Lingyan Ping, Caroline M. Watson, Duc M. Duong, Eric B. Dammer, Erik C. B. Johnson, Blaine R. Roberts, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Summary: Despite being at higher risk for Alzheimer's disease, African Americans have been underrepresented in AD research. This study used proteomic profiling to identify common and divergent AD biomarkers in the cerebrospinal fluid of African Americans and Caucasians.
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Janina Krell-Roesch, Martin Rakusa, Jeremy A. Syrjanen, Argonde C. van Harten, Val J. Lowe, Clifford R. Jack, Walter K. Kremers, David S. Knopman, Gorazd B. Stokin, Ronald C. Petersen, Maria Vassilaki, Yonas E. Geda
Summary: This study examined the association between CSF biomarkers of Alzheimer's disease and neuropsychiatric symptoms in older non-demented adults. The results showed that lower CSF Aβ42 and higher t-tau/Aβ42 and p-tau/Aβ42 ratios were associated with depression, anxiety, and other NPS.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Michio Senda, K. Ishii, K. Ito, T. Ikeuchi, H. Matsuda, T. Iwatsubo, A. Iwata, R. Ihara, K. Suzuki, K. Kasuga, Y. Ikari, Y. Niimi, H. Arai, A. Tamaoka, Y. Arahata, Y. Itoh, H. Tachibana, Y. Ichimiya, S. Washizuka, T. Odawara, K. Ishii, K. Ono, T. Yokota, A. Nakanishi, E. Matsubara, H. Mori, H. Shimada
Summary: The study evaluated biomarkers in Japanese cognitively unimpaired and early/late MCI patients, finding discrepancies in amyloid and tau results between PET and CSF. The positivity rates and relationship between amyloid and tau were consistent with previous reports.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2021)
Article
Medicine, Research & Experimental
Juan Lantero-Rodriguez, Anniina Snellman, Andrea L. Benedet, Marta Mila-Aloma, Elena Camporesi, Laia Montoliu-Gaya, Nicholas J. Ashton, Agathe Vrillon, Thomas K. Karikari, Juan Domingo Gispert, Gemma Salvado, Mahnaz Shekari, Christina E. Toomey, Tammaryn L. Lashley, Henrik Zetterberg, Marc Suarez-Calvet, Gunnar Brinkmalm, Pedro Rosa Neto, Kaj Blennow
Summary: Alzheimer's disease has a long preclinical phase and requires biomarkers for early pathological changes. P-tau235 may be a key feature and staging biomarker. A new CSF p-tau235 assay shows promise in clinical research.
EMBO MOLECULAR MEDICINE
(2021)
Article
Medicine, Research & Experimental
Rik Ossenkoppele, Juhan Reimand, Ruben Smith, Antoine Leuzy, Olof Strandberg, Sebastian Palmqvist, Erik Stomrud, Henrik Zetterberg, Philip Scheltens, Jeffrey L. Dage, Femke Bouwman, Kaj Blennow, Niklas Mattsson-Carlgren, Shorena Janelidze, Oskar Hansson
Summary: The study found that biomarkers of tau pathology may be differently associated with various factors related to Alzheimer's disease. CSF and plasma p-tau181 and p-tau217 levels are more closely linked to early markers of the disease, while tau-PET shows stronger associations with cognitive and neurodegenerative markers of disease progression.
EMBO MOLECULAR MEDICINE
(2021)
Article
Geriatrics & Gerontology
Ingmar Skoog, Silke Kern, Jenna Najar, Rita Guerreiro, Jose Bras, Margda Waern, Henrik Zetterberg, Kaj Blennow, Anna Zettergren
Summary: This study found that genetic risk of AD beyond the APOE locus is associated with NfL in individuals without A beta 42 pathology, and with A beta 42 in APOE epsilon 4 carriers, suggesting these associations are driven by different mechanisms in cognitively healthy 70-year olds from the general population.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(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
Clinical Neurology
Lei Liu, Bianca M. Lauro, Amy He, Hyo Lee, Sanjay Bhattarai, Michael S. Wolfe, David A. Bennett, Celeste M. Karch, Tracy Young-Pearse, Dennis J. Selkoe
Summary: This study aims to identify biomarkers for Alzheimer's disease (AD) and finds that the A beta 37/42 ratio can be used to distinguish AD from normal aging. Experimental results show that this ratio outperforms the traditional ratio in differentiating physiological and pathological states in cell culture, brain tissue, and cerebrospinal fluid. The findings may provide a new indicator for early diagnosis of AD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Kanta Horie, Nicolas R. Barthelemy, Chihiro Sato, Randall J. Bateman
Summary: The study analyzed MTBR-Tau species in Alzheimer's disease and control CSF using sequential immunoprecipitation and chemical extraction methods followed by mass spectrometry. The species containing the region beginning at residue 243 were found to be highly correlated with tau PET and cognitive measures. This suggests that CSF level of tau species containing the upstream region of MTBR may serve as biomarkers to stage Alzheimer's disease and track the development of tau-directed therapeutics.
Article
Clinical Neurology
Kanta Horie, Nicolas R. Barthelemy, Chihiro Sato, Randall J. Bateman
Summary: The study analyzed MTBR-tau species in CSF and found that tau species containing the upstream region of MTBR were highly correlated with tau PET and cognitive assessments in Alzheimer's disease, suggesting they could serve as biomarkers for staging Alzheimer's disease and tracking tau-directed therapeutics development.
Article
Clinical Neurology
Zachary Winder, Tiffany L. Sudduth, Sonya Anderson, Ela Patel, Janna Neltner, Barbara J. Martin, Katherine E. Snyder, Erin L. Abner, Gregory A. Jicha, Peter T. Nelson, Donna M. Wilcock
Summary: The study evaluated the relationship between plasma biomarkers and neuropathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID). The results showed certain plasma biomarkers were associated with AD and VCID pathology, providing support for further research in using plasma biomarkers as a clinical screening tool.
ALZHEIMERS & DEMENTIA
(2023)
Review
Biochemistry & Molecular Biology
Brian J. Lopresti, Sarah K. Royse, Chester A. Mathis, Savannah A. Tollefson, Rajesh Narendran
Summary: With the emergence of PET, psychiatry gained access to a non-invasive tool for assessing human brain function. Early applications focused on measuring blood flow and metabolism, but specific probes for dopamine and serotonin receptors were later developed. However, the development of monoamine-enhancing drugs was not very successful, leading to a shift in drug development towards other targets. In recent years, PET imaging techniques have also been developed for studying non-monoamine targets.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Sarah K. Royse, Brian J. Lopresti, Chester A. Mathis, Savannah Tollefson, Rajesh Narendran
Summary: Early PET applications in psychiatry aimed to identify cerebral blood flow and metabolism abnormalities, but the need for more specific neurochemical imaging probes became evident. The development of monoaminergic PET radiopharmaceuticals was driven by the belief in the centrality of monoamine dysfunction in psychiatric disorders. However, as drug development shifted away from monoamines, new PET imaging agents for non-monoamine targets were developed. Part two of the review focuses on clinical research studies using these novel targets and radiotracers across different psychiatric disorders.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Geriatrics & Gerontology
Minjie Wu, Noah Schweitzer, Bistra E. Iordanova, Edythe Halligan-Eddy, Dana L. Tudorascu, Chester A. Mathis, Brian J. Lopresti, M. Ilyas Kamboh, Ann D. Cohen, Beth E. Snitz, William E. Klunk, Howard J. Aizenstein
Summary: This study explored the interactive effects of small vessel disease (SVD) and amyloid-beta (Aβ) pathology on hippocampal functional connectivity and volume in cognitively normal older adults. The results showed that in older adults with white matter hyperintensities (WMH+), higher Aβ burden was associated with increased hippocampal local connectivity and lower gray matter density in the medial temporal lobe (MTL). In older adults without WMH, higher Aβ burden was associated with increased hippocampal distal connectivity and no changes in MTL gray matter density. These findings provide support for a hippocampal excitotoxicity model linking SVD to neurodegeneration and the progression to Alzheimer's disease (AD).
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Constantinos Constantinides, Laura K. M. Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M. Diaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T. Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A. Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Victor Ortiz-Garcia de la Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quide, Paul E. Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarro, Ulrich Schall, Andre Schmidt, Rodney J. Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia Thomopoulos, David Tomecek, Alexander S. Tomyshev, Diana Tordesillas-Gutierrez, Therese van Amelsvoort, Javier Vazquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S. Weickert, Thomas Weickert, Paul M. Thompson, Lianne Schmaal, Theo G. M. van Erp, Jessica Turner, James H. Cole, Danai Dima, Esther Walton
Summary: Schizophrenia patients show evidence of advanced brain ageing, which is not associated with clinical characteristics.
MOLECULAR PSYCHIATRY
(2023)
Article
Biology
Nirmal Verma, Gopal Viswanathan Velmurugan, Edric Winford, Han Coburn, Deepak Kotiya, Noah Leibold, Laura Radulescu, Sanda Despa, Kuey C. Chen, Linda J. Van Eldik, Peter T. Nelson, Donna M. Wilcock, Gregory A. Jicha, Ann M. Stowe, Larry B. Goldstein, David K. Powel, Jeffrey H. Walton, Manuel F. Navedo, Matthew A. Nystoriak, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Florin Despa
Summary: Impairment of vascular pathways contributes to Alzheimer's disease. Blood amylin secreted from the pancreas perturbs cerebral A beta clearance, leading to amylin and A beta co-deposits in the brain microvasculature. Altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and A beta pathology.
COMMUNICATIONS BIOLOGY
(2023)
Article
Neurosciences
Marlena Duda, Armin Iraji, Judith M. Ford, Kelvin O. Lim, Daniel H. Mathalon, Bryon A. Mueller, Steven G. Potkin, Adrian Preda, Theo G. M. Van Erp, Vince D. Calhoun
Summary: By using spatially constrained independent component analysis (scICA), this study found that rsfMRI scans of just 2-5 minutes can provide good clinical utility without significant loss of individual functional network connectivity (FNC) information from longer scan lengths.
HUMAN BRAIN MAPPING
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Bieneke Janssen, Guilong Tian, Zsofia Lengyel-Zhand, Chia-Ju Hsieh, Marshall G. Lougee, Aladdin Riad, Kuiying Xu, Catherine Hou, Chi-Chang Weng, Brian J. Lopresti, Hee Jong Kim, Vinayak V. Pagar, John J. Ferrie, Benjamin A. Garcia, Chester A. Mathis, Kelvin Luk, E. James Petersson, Robert H. Mach
Summary: In this study, a new radioligand with high affinity (<10 nM) for α-synuclein fibrils and PD tissue was identified through a similarity search. This study suggests that a simple in silico approach is a promising strategy to identify novel ligands for target proteins in the CNS and can be radiolabeled for PET neuroimaging studies.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Neurosciences
Deniz Alacam, Robyn Miller, Oktay Agcaoglu, Adrian Preda, Judith Ford, Vince Calhoun
Summary: In this study, a framework was proposed to analyze time-resolved spectral coupling among different brain circuits using independent component analysis. The results showed significant differences in visual network connectivity and spectral power profiles between people with schizophrenia and healthy controls. This approach can be useful in understanding the underlying causes of impaired visual processing in schizophrenia.
FRONTIERS IN NEUROSCIENCE
(2023)
Editorial Material
Pharmacology & Pharmacy
Adrian Preda
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Justin R. Deters, Alexandra C. Fietsam, Phillip E. Gander, Laura L. Boles L. Ponto, Thorsten Rudroff
Summary: Combining MRI and PET imaging with FDG can provide a comprehensive overview of the effects of PCS on brain volumes and metabolism. This study found differences in MRI/PET outcomes between individuals <6 months and >6 months post-COVID-19, as well as associations between these outcomes and fatigue symptoms.
Article
Clinical Neurology
Matthew D. Zammit, Tobey J. Betthauser, Andrew K. Mcvea, Charles M. Laymon, Dana L. Tudorascu, Sterling C. Johnson, Sigan L. Hartley, Alexander K. Converse, Davneet S. Minhas, Shahid H. Zaman, Beau M. Ances, Charles K. Stone, Chester A. Mathis, Annie D. Cohen, William E. Klunk, Benjamin L. Handen, Bradley T. Christian
Summary: Understanding the trajectories of AD biomarkers in individuals with Down syndrome (DS) is crucial for clinical interventions and interpretation of drug-related changes.
ALZHEIMERS & DEMENTIA
(2023)
Review
Clinical Neurology
Atri Chatterjee, Veronica Hirsch-Reinshagen, Imogene Scott, Neil Cashman, Ging-Yuek Robin Hsiung
Summary: This study conducted a systematic review and found that the frequency of psychosis in FTD patients was 24.2%. Among the genetic mutation carriers, C9orf72 mutation carriers had the highest frequency of psychosis (31.4%), while GRN and MAPT mutation carriers had lower frequencies of psychosis. Among the pathological subtypes, patients with FUS pathology, TDP-43 pathology, and tau pathology had a prevalence of psychosis at 30%, 25.3%, and 16.4% respectively.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Neurosciences
A. Iraji, Z. Fu, A. Faghiri, M. Duda, J. Chen, S. Rachakonda, T. DeRamus, P. Kochunov, B. M. Adhikari, A. Belger, J. M. Ford, D. H. Mathalon, G. D. Pearlson, S. G. Potkin, A. Preda, J. A. Turner, T. G. M. van Erp, J. R. Bustillo, K. Yang, K. Ishizuka, A. Faria, A. Sawa, K. Hutchison, E. A. Osuch, J. Theberge, C. Abbott, B. A. Mueller, D. Zhi, C. Zhuo, S. Liu, Y. Xu, M. Salman, J. Liu, Y. Du, J. Sui, T. Adali, V. D. Calhoun
Summary: This study identifies replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates using rsfMRI data from over 100k individuals through multi-model-order independent component analysis (ICA). The feasibility of estimating subject-specific ICNs via spatially constrained ICA is also studied. The results show that subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. Longer scans may not always be desirable and spatial smoothness should be considered in optimizing data length.
HUMAN BRAIN MAPPING
(2023)
Article
Psychiatry
Akiko Mizuno, Helmet Talib Karim, Maria J. Ly, Brian J. Lopresti, Ann D. Cohen, Areej A. Ali, Chester A. Mathis, William E. Klunk, Howard J. Aizenstein, Beth E. Snitz
Summary: The study aimed to explore the symptoms of subjective cognitive decline (SCD) using fMRI brain activity and investigate the association with amyloid-beta (Ass) load. The results showed that SCD severity was associated with lower dorsomedial thalamus activation.
FRONTIERS IN PSYCHIATRY
(2023)