Article
Biochemistry & Molecular Biology
Marina Arcaro, Chiara Fenoglio, Maria Serpente, Andrea Arighi, Giorgio G. Fumagalli, Luca Sacchi, Stefano Floro, Marianna D'Anca, Federica Sorrentino, Caterina Visconte, Alberto Perego, Elio Scarpini, Daniela Galimberti
Summary: This study compared the application of ELISA and CLEIA methods for detecting cerebrospinal fluid biomarkers. The results demonstrated that CLEIA method had higher accuracy and better automation, which could potentially be useful in clinical diagnosis and studies.
Article
Medicine, General & Internal
Helena Sophia Gleerup, Camilla Steen Jensen, Peter Hogh, Steen Gregers Hasselbalch, Anja Hviid Simonsen
Summary: This study evaluated the levels of lactoferrin in cerebrospinal fluid (CSF) and saliva in a cohort of patients with neurodegenerative dementias, finding that lactoferrin could not differentiate between diagnostic groups. Additionally, no significant relationships were found between lactoferrin levels and tau, phosphorylated tau (p-tau), and amyloid 1-42 (A beta(42)) in CSF.
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.
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
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
Clinical Neurology
Wei Zhang, Juan I. Young, Lissette Gomez, Michael A. Schmidt, David Lukacsovich, Achintya Varma, X. Steven Chen, Eden R. Martin, Lily Wang
Summary: This study demonstrates the association between DNA methylation (DNAm) in blood and cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD). The findings suggest that changes in pathological processes in the CSF can be reflected in the blood epigenome, providing valuable insights for mechanistic and biomarker studies of AD.
ALZHEIMERS RESEARCH & THERAPY
(2023)
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
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
Multidisciplinary Sciences
Timo Eninger, Stephan A. Mueller, Mehtap Bacioglu, Manuel Schweighauser, Marius Lambert, Luis F. Maia, Jonas J. Neher, Sarah M. Hornfeck, Ulrike Obermueller, Gernot Kleinberger, Christian Haass, Philipp J. Kahle, Matthias Staufenbiel, Lingyan Ping, Duc M. Duong, Allan Levey, Nicholas T. Seyfried, Stefan F. Lichtenthaler, Mathias Jucker, Stephan A. Kaeser
Summary: Single-cell transcriptomics has revealed glial activation states associated with neurodegenerative diseases, but little is known about biomarker changes in bodily fluids. This study explored proteomic changes in cerebrospinal fluid related to proteopathic lesions in mouse models and found increased glial-derived proteins that could also be detected in human cerebrospinal fluid, supporting efforts to identify fluid biomarkers for neurodegenerative diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Geriatrics & Gerontology
Xun Gong, Hantao Zhang, Xiaoyan Liu, Yi Liu, Junlin Liu, Funmilayo O. Fapohunda, Peng Lue, Kun Wang, Min Tang
Summary: Liquid biopsy has made great progress in the preclinical diagnosis and clinical practice for Alzheimer's disease (AD). It provides a fast, low-cost, and easy way to diagnose AD and has led to the discovery of various biomarkers and a better understanding of the molecular pathogenesis of AD. However, the weighing of liquid biopsy reports for preclinical AD diagnosis remains an ongoing question.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Medicine, General & Internal
Cristina M. Pedrero-Prieto, Javier Frontinan-Rubio, Francisco J. Alcain, Mario Duran-Prado, Juan R. Peinado, Yoana Rabanal-Ruiz
Summary: CSF is considered the best target for biomarker discovery in neurodegenerative diseases due to its deep irrigation of the brain and ease of sample extraction. Discoveries of new proteins in CSF have identified important biomarkers related to AD, and deeper analysis of data from multiple proteomic studies may reveal disrupted components or metabolic pathways in AD.
Article
Clinical Neurology
Caterina Motta, Martina Assogna, Chiara Giuseppina Bonomi, Francesco Di Lorenzo, Marzia Nuccetelli, Nicola Biagio Mercuri, Giacomo Koch, Alessandro Martorana
Summary: The levels of catecholaminergic enzymes in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) were analyzed. It was found that AD patients had lower levels of dopamine/norepinephrine (DA/NA) innervation markers, but increased levels of dopamine-beta-hydroxylase (D beta H). These findings indicate a close association between catecholaminergic enzymes and the neurodegenerative and neuroinflammatory processes in AD pathology.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
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
Health Care Sciences & Services
Fernando Arreola, Benjamin Salazar, Antonio Martinez
Summary: This study analyzed the viability of asymmetry-related measures as potential biomarkers for early diagnosis of Alzheimer's Disease. The results showed that these measures differentiated themselves temporally before most of the other evaluated biomarkers, suggesting the need for further studies to confirm these findings.
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
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
Patrick H. Luckett, Charlie Chen, Brian A. Gordon, Julie Wisch, Sarah B. Berman, Jasmeer P. Chhatwal, Carlos Cruchaga, Anne M. Fagan, Martin R. Farlow, Nick C. Fox, Mathias Jucker, Johannes Levin, Colin L. Masters, Hiroshi Mori, James M. Noble, Stephen Salloway, Peter R. Schofield, Adam M. Brickman, William S. Brooks, David M. Cash, Michael J. Fulham, Bernardino Ghetti, Clifford R. Jack, Jonathan Voeglein, William E. Klunk, Robert Koeppe, Yi Su, Michael Weiner, Qing Wang, Daniel Marcus, Deborah Koudelis, Nelly Joseph-Mathurin, Lisa Cash, Russ Hornbeck, Chengjie Xiong, Richard J. Perrin, Celeste M. Karch, Jason Hassenstab, Eric McDade, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances
Summary: This study analyzed 19 biomarkers of Alzheimer's disease using hierarchical clustering and feature selection, and found that amyloid and tau measures were the primary predictors. Emerging biomarkers of neuronal integrity and inflammation showed weaker predictive ability.
ALZHEIMERS & DEMENTIA
(2023)
Article
Geriatrics & Gerontology
Juraj Sprung, Mariana L. Laporta, David S. Knopman, Ronald C. Petersen, Michelle M. Mielke, Clifford R. Jack, David P. Martin, Andrew C. Hanson, Darrell R. Schroeder, Phillip J. Schulte, Scott A. Przybelski, Diana J. Valencia Morales, Toby N. Weingarten, Prashanthi Vemuri, David O. Warner
Summary: This study found that hospitalization in older adults is associated with accelerated cortical thinning, amyloid accumulation, and white matter hyperintensities (WMH) increases, especially in medical hospitalizations. However, these changes were modest and did not translate to an increased risk of crossing the abnormality threshold.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Geriatrics & Gerontology
Emma L. Ducca, Gabriela T. Gomez, Priya Palta, Kevin J. Sullivan, Clifford R. Jack, David S. Knopman, Rebecca F. Gottesman, Jeremy Walston, B. Gwen Windham, Keenan A. Walker
Summary: The study found a strong association between cerebral white matter structure and current and future frailty. Specifically, white matter hyperintensity volume was significantly associated with frailty. However, measures of white matter microstructure were not generally associated with progression from nonfrail to frail status.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Geriatrics & Gerontology
B. Gwen Windham, Michael E. Griswold, Radhikesh Ranadive, Kevin Sullivan, Thomas H. Mosley, Michelle M. Mielke, Clifford R. Jack, Dave Knopman, Ron Petersen, Prashanthi Vemuri
Summary: This study aimed to examine if the association between cerebral perfusion and gait speed is influenced by systolic blood pressure and age. The results showed that poorer cerebral perfusion is associated with slower gait speeds, particularly with older age, while higher perfusion can significantly attenuate age-related differences in gait speed.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Oncology
Firat Kara, Christine M. Lohse, Anna M. Castillo, Nirubol Tosakulwong, Timothy G. Lesnick, Clifford R. Jack, Ronald C. Petersen, Janet E. Olson, Fergus J. Couch, Kathryn J. Ruddy, Kejal Kantarci, Michelle M. Mielke
Summary: This study aimed to investigate whether the use of selective estrogen receptor modifiers (SERMs), including tamoxifen and raloxifene, was associated with cognitive performance and markers of neurodegeneration associated with Alzheimer's disease. The results showed no significant associations between the use of SERMs and cognition or MCI in both breast cancer patients and women without a history of cancer.
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
Clinical Neurology
Vijay K. Ramanan, Robel K. Gebre, Jonathan Graff-Radford, Ekaterina Hofrenning, Alicia Algeciras-Schimnich, Daniel J. Figdore, Val J. Lowe, Michelle M. Mielke, David S. Knopman, Owen A. Ross, Clifford R. Jack Jr, Ronald C. Petersen, Prashanthi Vemuri
Summary: Ramanan et al. found that integrating genetic risk scores improves the diagnostic value of plasma biomarkers for Alzheimer's disease, especially in predicting amyloid PET positivity. However, more advances are needed before these biomarkers can be widely used. By analyzing a large sample, they discovered that the AD-GRS is independently associated with amyloid PET levels and significantly enhances the classification accuracy of amyloid PET positivity when combined with high plasma p-tau(181). Machine learning methods that incorporate plasma biomarkers, demographics, and the AD-GRS show high accuracy in predicting amyloid PET levels.
Article
Clinical Neurology
Diego Z. Carvalho, Stuart J. McCarter, Erik K. St Louis, Scott A. Przybelski, Kohl Johnson L. Sparrman, Virend K. Somers, Bradley F. Boeve, Ronald C. Petersen, Clifford R. Jack Jr, Jonathan Graff-Radford, Prashanthi Vemuri
Summary: This study aimed to investigate the association between polysomnographic (PSG) sleep parameters and neuroimaging biomarkers of cerebrovascular disease (CVD) in older adults with obstructive sleep apnea (OSA). The results showed that reduced slow-wave sleep and severe OSA were associated with increased burden of white matter abnormalities in older adults, which may contribute to a higher risk of cognitive impairment, dementia, and stroke.
Article
Clinical Neurology
Sanaz Sedaghat, Yuekai Ji, Jean-Philippe Empana, Timothy M. Hughes, Thomas H. Mosley, Rebecca F. Gottesman, Michael Griswold, Clifford R. Jack, Pamela L. Lutsey, Thomas T. van Sloten
Summary: This study aimed to investigate the association of cardiovascular health in midlife and late-life as well as changes in cardiovascular health between these periods with the prevalence of cerebral vascular disease in late-life. The results showed that better cardiovascular health in midlife, improvement of cardiovascular health within midlife, higher cardiovascular health at late-life, and improvement of cardiovascular health from midlife to late-life were associated with a lower prevalence of cerebral vascular disease markers in late-life. Therefore, improving cardiovascular health in midlife and late-life may help prevent the development of cerebral vascular disease.
Article
Neurosciences
Nicole S. McKay, Brian A. Gordon, Russ C. Hornbeck, Aylin Dincer, Shaney Flores, Sarah J. Keefe, Nelly Joseph-Mathurin, Clifford R. Jack, Robert Koeppe, Peter R. Millar, Beau M. Ances, Charles D. Chen, Alisha Daniels, Diana A. Hobbs, Kelley Jackson, Deborah Koudelis, Parinaz Massoumzadeh, Austin McCullough, Michael L. Nickels, Farzaneh Rahmani, Laura Swisher, Qing Wang, Ricardo F. Allegri, Sarah B. Berman, Adam M. Brickman, William S. Brooks, David M. Cash, Jasmeer P. Chhatwal, Gregory S. Day, Martin R. Farlow, Christian la Fougere, Nick C. Fox, Michael Fulham, Bernardino Ghetti, Neill Graff-Radford, Takeshi Ikeuchi, William Klunk, Jae-Hong Lee, Johannes Levin, Ralph Martins, Colin L. Masters, Jonathan McConathy, Hiroshi Mori, James Noble, Gerald Reischl, Christopher Rowe, Stephen Salloway, Raquel Sanchez-Valle, Peter R. Schofield, Hiroyuki Shimada, Mikio Shoji, Yi Su, Kazushi Suzuki, Jonathan Voeglein, Igor Yakushev, Carlos Cruchaga, Jason Hassenstab, Celeste Karch, Eric McDade, Richard J. Perrin, Chengjie Xiong, John C. Morris, Randall J. Bateman, Tammie L. S. Benzinger
Summary: The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration that studies autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations in three genes. Non-carrier siblings from ADAD families can be recruited for case-control studies. The predictable age of onset in ADAD allows for mapping candidate AD biomarkers during the preclinical phase. This study provides valuable data for understanding early disease stages of both ADAD and sporadic AD, as well as for research in healthy aging.
NATURE NEUROSCIENCE
(2023)
Article
Clinical Neurology
Srishti Shrestha, Xiaoqian Zhu, Kevin J. Sullivan, Chad Blackshear, Jennifer A. Deal, A. Richey Sharrett, Vidyulata Kamath, Andrea L. C. Schneider, Clifford R. Jack, Juebin Huang, Priya Palta, Robert I. Reid, David S. Knopman, Rebecca F. Gottesman, Honglei Chen, B. Gwen Windham, Michael E. Griswold, Jr Thomas H. Mosley
Summary: Research shows that neuronal microstructural integrity in multiple brain regions, particularly the medial temporal lobe (MTL), is associated with odor identification ability. The associations between microstructural integrity and olfaction are stronger in individuals with mild cognitive impairment (MCI) compared to those with normal cognition, suggesting different effects of dementia pathogenesis.
Article
Clinical Neurology
Keenan A. Walker, Ron C. Hoogeveen, Aaron R. Folsom, Christie M. Ballantyne, David S. Knopman, B. Gwen Windham, Clifford R. Jack Jr, Rebecca F. Gottesman
Summary: In the article "Midlife Systemic Inflammatory Markers Are Associated With Late-Life Brain Volume: The ARIC Study" by Walker et al., coding errors were found to have affected the statistical analyses. The authors have corrected the errors and reanalyzed the data, stating that the errors did not change the overall message of the article. The identified errors include misclassification of a nominal covariate, use of incorrect alcohol use covariate, and an error in the scaling of beta coefficients.
Article
Clinical Neurology
Rioghna R. Pittock, Jeremiah A. Aakre, Anna M. Castillo, Vijay K. Ramanan, Walter K. Kremers, Clifford R. Jack Jr, Prashanthi Vemuri, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Jonathan Graff-Radford, Maria Vassilaki
Summary: Treatment options for Alzheimer's disease are limited, and research on the applicability of anti-beta-amyloid monoclonal antibodies in the general population is lacking. This study aims to assess the generalizability of anti-amyloid treatment and apply the eligibility criteria of two clinical trials to a population-based sample.