Article
Radiology, Nuclear Medicine & Medical Imaging
Colin Groot, Sylvia Villeneuve, Ruben Smith, Oskar Hansson, Rik Ossenkoppele
Summary: The introduction of PET ligands that bind tau pathology has allowed for the quantification and visualization of tau pathology in aging and Alzheimer's disease. While these ligands are effective in binding tau aggregates in advanced stages of AD, their binding in non-AD tauopathies is weaker and overlaps with known off-target binding regions. An increased neocortical tau PET signal holds important prognostic information, and tau PET shows great potential as a prognostic marker in symptomatic stages of AD. For differential diagnosis, tau PET is primarily useful in distinguishing AD dementia from other neurodegenerative diseases, but its performance decreases in the mild cognitive impairment stage of AD.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Mei Tian, Xuexin He, Chentao Jin, Xiao He, Shuang Wu, Rui Zhou, Xiaohui Zhang, Kai Zhang, Weizhong Gu, Jing Wang, Hong Zhang
Summary: Pathology is a medical specialty focused on studying the nature and causes of disease, and plays a crucial role in connecting basic research and clinical medicine. Challenges such as invasiveness and sample representativeness limitations exist in traditional pathology, while molecular imaging provides a noninvasive way to visualize and measure biological processes at the molecular level. A new pathophysiology visualization system based on molecular imaging is showing great potential in reforming pathological practice, driving improvements in trans-scale imaging, transparency, and translation processes.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Chemistry, Analytical
Xueluer Mu, Fapu Wu, Rui Wang, Zejian Huang, Taoyuze Lv, Yingxi Lu, Bin Liu, Xianfeng Zhou
Summary: A cyanine-derived NIR molecular rotor Mu1 with ratiometric signal is introduced, showing significant enhancement in fluorescence ratio in the presence of insulin fibrils. This sensor may be promising for early detection of AD, as the enhancement in fluorescence ratio is due to restricted rotation and conformational factors.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Clinical Neurology
Yulong Xu, Zude Chen, Hsiao-Ying Wey, Yingxia Liang, Rudolph E. Tanzi, Can Zhang, Changning Wang
Summary: The study developed a new tracer to visualize SIRT1 in the brains related to aging and AD, displaying the ability to accurately show SIRT1 in AD transgenic mice for the first time. This tracer can provide insights into the neuroanatomical mechanisms of AD and potential biomarkers for aging-related changes in the brain.
ALZHEIMERS & DEMENTIA
(2021)
Review
Clinical Neurology
Alessia Filippone, Domenico Pratico
Summary: Intracellular protein trafficking through the endosomes is crucial for normal neuronal function. Dysfunctions in the endosome system, particularly through the recycling, degradation, and retrograde pathways, are common in neurodegenerative diseases like Alzheimer's and Down syndrome. Two major routes, mediated by the retromer complex and the newly discovered retriever system, play key roles in endosomal transport and could be potential therapeutic targets in these diseases.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Yanxing Chen, Shuai Zhao, Ziqi Fan, Zheyu Li, Yueli Zhu, Ting Shen, Kaicheng Li, Yaping Yan, Jun Tian, Zhirong Liu, Baorong Zhang
Summary: The study uncovered a crosstalk between amyloid and NP tau pathology, where Aβ plaques promoted the aggregation of NP tau, and metformin enhanced microglial autophagy capability to promote the phagocytosis of pathological Aβ and tau proteins, reducing Aβ deposits and limiting the spreading of NP tau pathology.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Shashank Raj, Sameer Vyas, Manish Modi, Gaurav Garg, Paramjeet Singh, Ajay Kumar, Chirag Kamal Ahuja, Manoj K. Goyal, Varan Govind
Summary: This study compared the evaluation of microstructural changes in the brains of AzD patients using diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) with a whole-brain atlas. The results showed widespread microstructural changes in both white matter (WM) and gray matter (GM) in AzD patients, which were effectively depicted by both DKI and DTI. However, the alterations in kurtosis parameters were more limited and correlated with areas in the brain primarily involved in cognition.
ACADEMIC RADIOLOGY
(2022)
Review
Chemistry, Analytical
Xingyun Liu, Yibiao Liu, Qiong Liu
Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. Early diagnosis is crucial for intervention and treatment effectiveness assessment, but current clinical methods are costly and inaccessible. Blood sample detection offers a less invasive and more accessible alternative, with various assays developed for the detection of AD biomarkers. Fluorescence-sensing techniques, with their low toxicity and high sensitivity, can not only detect biomarker levels in blood but also image them in the brain in real time. This review summarizes the recent development of fluorescent sensing platforms and their potential clinical applications.
Article
Radiology, Nuclear Medicine & Medical Imaging
Brian J. Burkett, Jeffrey C. Babcock, Val J. Lowe, Jonathan Graff-Radford, Rathan M. Subramaniam, Derek R. Johnson
Summary: PET imaging plays an essential role in the earlier and more specific diagnoses of dementia syndromes, especially with the development of pathology-specific disease-modifying therapy for Alzheimer disease. Amyloid and tau PET techniques have entered clinical use, making nuclear medicine physicians and radiologists crucial members of the care team. This review discusses recent changes in the understanding of dementia and examines the roles of nuclear medicine imaging in clinical practice.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Clinical Neurology
Emily J. Davis, Caroline W. Solsberg, Charles C. White, Elena Minones-Moyano, Marina Sirota, Lori Chibnik, David A. Bennett, Philip L. De Jager, Jennifer S. Yokoyama, Dena B. Dubal
Summary: This study found that X chromosome gene expression is associated with cognitive change and tau pathology in aging and AD in a sex-specific manner, with cognitive change related to X chromosome gene expression in women and tau pathology related to X chromosome gene expression in men.
Article
Clinical Neurology
Prashanthi Vemuri, Charles Decarli, Marco Duering
Summary: This focused review provides an update on current magnetic resonance imaging methods for measuring cerebrovascular disease lesions and early cerebrovascular disease-related brain injury. It discusses the clinical implications and relevance of these imaging markers for cognitive decline, incident dementia, and disease progression in Alzheimer's disease and related dementias. The review also presents the outlook and challenges in the field.
Article
Chemistry, Analytical
Ying Tu, Keke Chai, Junjie Wu, Yuan Hu, Shuo Shi, Danjing Yang, Tianming Yao
Summary: The aggregation of Tau proteins is closely related to the progression and severity of Alzheimer's disease. Developing selective imaging probes for Tau aggregates is challenging. This study designed three new fluorescent dyes and demonstrated the importance of side chain substitution in improving the selectivity of Tau probes.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Clinical Neurology
Edmarie Guzman-Velez, Henrik Zetterberg, Joshua T. Fox-Fuller, Clara Vila-Castelar, Justin S. Sanchez, Ana Baena, Gloria Garcia-Ospina, David Aguillon, Enmanuelle Pardilla-Delgado, Jennifer R. Gatchel, Reisa A. Sperling, Keith Johnson, Eric M. Reiman, Kaj Blennow, Francisco Lopera, Yakeel T. Quiroz
Summary: This study found that plasma NfL levels are associated with higher tau burden and worse cognition in PSEN1 E280A mutation carriers. However, they are not related to amyloid beta load. After adjusting for age, elevated plasma NfL levels are only correlated with worse memory recall.
ALZHEIMERS & DEMENTIA
(2021)
Article
Neurosciences
Claudia Duran-Aniotz, Ines Moreno-Gonzalez, Nazaret Gamez, Nelson Perez-Urrutia, Laura Vegas-Gomez, Claudio Soto, Rodrigo Morales
Summary: Diverse patterns of misfolded protein deposition in Alzheimer's disease brains may lead to different phenotypes in recipient mice, suggesting that AD-subtypes are encoded in disease-associated amyloid-beta.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Erlon Ferreira Martin, Luiz Antonio Escorteganha Pollo, Layzon Antonio Lemos da Silva, Maique Weber Biavatti, Louis Pergaud Sandjo
Summary: Alzheimer's disease is a prevalent neurodegenerative disease, and a compound family called pyranochromenes has shown potential as inhibitors of acetylcholinesterase, making them promising candidates for the development of new drugs against Alzheimer's disease.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Clinical Neurology
Jonathan Voeglein, Nicolai Franzmeier, John C. Morris, Marianne Dieterich, Eric McDade, Mikael Simons, Oliver Preische, Anna Hofmann, Jason Hassenstab, Tammie L. Benzinger, Anne Fagan, James M. Noble, Sarah B. Berman, Neill R. Graff-Radford, Bernardino Ghetti, Martin R. Farlow, Jasmeer P. Chhatwal, Stephen Salloway, Chengjie Xiong, Celeste M. Karch, Nigel Cairns, Richard J. Perrin, Gregory Day, Ralph Martins, Raquel Sanchez-Valle, Hiroshi Mori, Hiroyuki Shimada, Takeshi Ikeuchi, Kazushi Suzuki, Peter R. Schofield, Colin L. Masters, Alison Goate, Virginia Buckles, Nick C. Fox, Patricio Chrem, Ricardo Allegri, John M. Ringman, Igor Yakushev, Christoph Laske, Mathias Jucker, Gunter Hoglinger, Randall J. Bateman, Adrian Danek, Johannes Levin
Summary: Autosomal dominant Alzheimer's disease (ADAD) has distinct neurological examination findings that are useful for estimating prognosis and guiding clinical care and therapeutic trial designs.
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)
Letter
Clinical Neurology
Antoinette O'Connor, Emily Abel, Andrea Lessa Benedet, Teresa Poole, Nicholas Ashton, Philip Simon John Weston, Amanda J. Heslegrave, Natalie Ryan, Suzie Barker, James M. Polke, Kaj Blennow, Henrik Zetterberg, Nick C. Fox
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Letter
Clinical Neurology
Erin Halley Squillacote Drazich-Taylor, Emily Todd, Rhian Convery, Martina Bocchetta, Mica Clarke, Jason D. Warren, Nick C. Fox, Tamas Revesz, Jonathan Daniel Rohrer
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Letter
Clinical Neurology
Antoinette O'Connor, Helen Rice, Josephine Barnes, Natalie S. Ryan, Kathy Y. Liu, Ricardo Francisco Allegri, Sarah Berman, John M. Ringman, Carlos Cruchaga, Martin R. Farlow, Jason Hassenstab, Jae-Hong Lee, Richard J. Perrin, Chengjie Xiong, Brian Gordon, Allan Levey, Alison Goate, Neil Graff-Radford, Johannes Levin, Mathias Jucker, Tammie Benzinger, Eric McDade, Hiroshi Mori, James M. Noble, Peter R. Schofield, Ralph N. Martins, Stephen Salloway, Jasmeer Chhatwal, John C. Morris, Randall Bateman, Rob Howard, Suzanne Reeves, Nick C. Fox
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Biology
Peter R. Millar, Brian A. Gordon, Patrick H. Luckett, Tammie L. S. Benzinger, Carlos Cruchaga, Anne M. Fagan, Jason J. Hassenstab, Richard J. Perrin, Suzanne E. Schindler, Ricardo F. Allegri, Gregory S. Day, Martin R. Farlow, Hiroshi Mori, Georg Nuebling, Randall J. Bateman, John C. Morris, Beau M. Ances
Summary: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.
Article
Cell Biology
Stephanie Schultz, Zahra P. Shirzadi, Aaron Schultz, Lei D. Liu, Colleen Fitzpatrick, Eric R. McDade, Nicolas Barthelemy, Alan Renton, Bianca Esposito, Nelly Joseph-Mathurin, Carlos D. Cruchaga, Charles Chen, Alison Goate, Ricardo Francisco Allegri, Tammie L. S. Benzinger, Sarah C. Berman, Helena M. Chui, Anne R. Fagan, Martin C. Farlow, Nick A. Fox, Brian S. Gordon, Gregory R. Day, Neill J. Graff-Radford, Jason J. Hassenstab, Bernard Hanseeuw, Anna R. Hofmann, Clifford R. Jack Jr, Mathias M. Jucker, Celeste A. Karch, Robert Koeppe, Jae-Hong I. Lee, Allan Levey, Johannes N. Levin, Ralph Martins, Hiroshi C. Mori, John Morris, James J. Noble, Richard Perrin, Pedro P. Rosa-Neto, Stephen Salloway, Raquel R. Sanchez-Valle, Peter Schofield, Chengjie A. Xiong, Keith J. Johnson, Randall A. Bateman, Reisa P. Sperling, Jasmeer Chhatwal
Summary: In individuals with autosomal-dominant Alzheimer disease (ADAD) caused by pathogenic variants in PSEN1, there is significant variability in the rates of cognitive decline and biomarker change. This study found that the location of the pathogenic variant within PSEN1 may contribute to this interindividual variability. Specifically, variants affecting the transmembrane domain of PSEN1 were associated with greater cognitive impairment, smaller hippocampal volume, and elevated phosphorylated tau levels compared to variants affecting the cytoplasmic domain.
Article
Geriatrics & Gerontology
Jemma Hazan, Simon Hall, Alex Pemberton, Ian Sherriffs, Suzanne Joels, Amanda Heslegrave, Elena Veleva, Mamoona Ghauri, Rhiannon Laban, Emily Abel, Henrik Zetterberg, Nick C. C. Fox, Robert Howard
Summary: This study explored the utility of plasma phosphorylated-tau181 (p-tau181) as a blood-based biomarker for Alzheimer's disease pathology. The results showed that 86% of clinicians found the p-tau181 result to be helpful and 44% of cases found it useful in making the diagnosis. However, further education and training are needed for clinicians to understand and interpret ambiguity in biomarker results.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Article
Clinical Neurology
Ellen Grober, Kellen K. Petersen, Richard B. Lipton, Jason Hassenstab, John C. Morris, Brian A. Gordon, Ali Ezzati
Summary: This study used the SOMI system to identify individuals with subtle cognitive impairment among those who appear to be cognitively normal. The results showed that participants with retrieval impairment (SOMI-1) had a higher incidence of cognitive impairment, and the risk increased even more for those with storage impairment (SOMI-3/4), after adjusting for demographics and APOE ε4 status. Additionally, the study found that SOMI remained a significant predictor of incident cognitive impairment even after considering biomarkers of β-amyloid, tau pathology, and neurodegeneration.
Article
Clinical Neurology
Rebecca E. Green, Jodie Lord, Marzia A. Scelsi, Jin Xu, Andrew Wong, Sarah Naomi-James, Alex Handy, Lachlan Gilchrist, Dylan M. Williams, Thomas D. Parker, Christopher A. Lane, Ian B. Malone, David M. Cash, Carole H. Sudre, William Coath, David L. Thomas, Sarah Keuss, Richard Dobson, Cristina Legido-Quigley, Nick C. Fox, Jonathan M. Schott, Marcus Richards, Petroula Proitsi
Summary: By analyzing the associations between blood metabolites and brain volume, hippocampal volume, and amyloid-beta status among the participants of Insight 46, this study identifies key metabolites related to brain health and preclinical pathology, providing insights into early disease mechanisms and potential intervention strategies.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Clinical Neurology
Antoinette O'Connor, David M. Cash, Teresa Poole, Pawel J. Markiewicz, Maggie R. Fraser, Ian B. Malone, Jieqing Jiao, Philip S. J. Weston, Shaney Flores, Russ Hornbeck, Eric McDade, Michael Schoell, Brian A. Gordon, Randall J. Bateman, Tammie L. S. Benzinger, Nick C. Fox
Summary: Cortical tau accumulation is a crucial pathological event in Alzheimer's disease, and understanding the timing and pattern of tau deposition can help track the disease progression. This study used data from participants in AD cohort studies to investigate if tau PET can detect early changes in presymptomatic carriers and found that there were regional differences in tau accumulation prior to symptom onset, particularly in posterior regions.
ALZHEIMERS RESEARCH & THERAPY
(2023)
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
Sarah-Naomi James, Emily N. Manning, Mathew Storey, Jennifer M. Nicholas, William Coath, Sarah E. Keuss, David M. Cash, Christopher A. Lane, Thomas Parker, Ashvini Keshavan, Sarah M. Buchanan, Aaron Wagen, Mathew Harris, Ian Malone, Kirsty Lu, Louisa P. Needham, Rebecca Street, David Thomas, John Dickson, Heidi Murray-Smith, Andrew Wong, Tamar Freiberger, Sebastian J. Crutch, Nick C. Fox, Marcus Richards, Frederik Barkhof, Carole H. Sudre, Josephine Barnes, Jonathan M. Schott
Summary: This study investigates the associations between normal-appearing white matter microstructural integrity, brain health, cognition, demographics, genetics, and cardiovascular health in cognitively normal adults in their seventies. The results show that measures of brain health, cognition, demographics, genetics, and cardiovascular health are associated with the microstructural integrity of normal-appearing white matter. Additionally, sex, blood pressure, and cardiovascular health in females were found to have an impact on white matter integrity.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
William Coath, Marc Modat, M. Jorge J. Cardoso, Pawel J. A. Markiewicz, Christopher A. D. Lane, Thomas D. Parker, Ashvini M. Keshavan, Sarah M. E. Buchanan, Sarah E. J. Keuss, Matthew J. Harris, Ninon Burgos, John Dickson, Anna L. Barnes, David L. Thomas, Daniel B. Beasley, Ian B. Malone, Andrew Wong, Kjell A. Erlandsson, Benjamin A. Thomas, Michael Scholl, Sebastien Ourselin, Marcus C. Richards, Nick C. M. Fox, Jonathan M. M. Schott, David M. Cash
Summary: The Centiloid scale aims to harmonize Aβ PET measures across different analysis methods. This study investigated the Centiloid transformation with PET/MRI data, finding that the transformation is valid but further understanding of the effects of acquisition or biological factors on using white matter as a reference is needed.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)
Article
Clinical Neurology
Julie K. K. Wisch, Ganesh M. Babulal, Kalen Petersen, Peter R. R. Millar, Enbal Shacham, Stephen Scroggins, Anna H. H. Boerwinkle, Shaney Flores, Sarah Keefe, Brian A. A. Gordon, John C. C. Morris, Beau M. M. Ances
Summary: This article presents a practical guide for applying geospatial methods to a neuroimaging cohort, aiming to evaluate the impact of the environment on the brain. The authors used structural magnetic resonance imaging data from 239 city-dwelling participants in St. Louis, Missouri, and compared them to population-level estimates from the American Community Survey to identify neighborhoods associated with altered brain structure. They observed a relationship between neighborhoods and brain health, suggesting the potential for neighborhood-based interventions.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)