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
Clinical Neurology
Johannes Levin, Jonathan Voglein, Yakeel T. Quiroz, Randall J. Bateman, Valentina Ghisays, Francisco Lopera, Eric McDade, Eric Reiman, Pierre N. Tariot, John C. Morris
Summary: The amyloid cascade hypothesis for Alzheimer's disease has faced challenges due to inconsistent clinical benefits of drugs targeting amyloid beta peptide. It is important to conduct intervention studies in cognitively unimpaired individuals at risk for dementia to further evaluate the hypothesis.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
John C. Morris, Michael Weiner, Chengjie Xiong, Laurel Beckett, Dean Coble, Naomi Saito, Paul S. Aisen, Ricardo Allegri, Tammie L. S. Benzinger, Sarah B. Berman, Nigel J. Cairns, Maria C. Carrillo, Helena C. Chui, Jasmeer P. Chhatwal, Carlos Cruchaga, Anne M. Fagan, Martin Farlow, Nick C. Fox, Bernardino Ghetti, Alison M. Goate, Brian A. Gordon, Neill Graff-Radford, Gregory S. Day, Jason Hassenstab, Takeshi Ikeuchi, Clifford R. Jack, William J. Jagust, Mathias Jucker, Johannes Levin, Parinaz Massoumzadeh, Colin L. Masters, Ralph Martins, Eric McDade, Hiroshi Mori, James M. Noble, Ronald C. Petersen, John M. Ringman, Stephen Salloway, Andrew J. Saykin, Peter R. Schofield, Leslie M. Shaw, Arthur W. Toga, John Q. Trojanowski, Jonathan Voeglein, Stacie Weninger, Randall J. Bateman, Virginia D. Buckles
Summary: This study compared biomarker changes in individuals with autosomal dominant Alzheimer's disease and late onset Alzheimer's disease and found similarities in their pathophysiology, suggesting a shared pathobiological construct.
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.
Review
Geriatrics & Gerontology
Qiongqiong Qiu
Summary: Alzheimer's disease is the most common form of dementia with no cure. Research on early biomarkers and functional connectivity changes in the brain is crucial for early detection and intervention.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Clinical Neurology
David Aguillon, Stephanie Langella, Yinghua Chen, Justin S. Sanchez, Yi Su, Clara Vila-Castelar, Daniel Vasquez, Henrik Zetterberg, Oskar Hansson, Jeffrey L. Dage, Shorena Janelidze, Kewei Chen, Joshua T. Fox-Fuller, Paula Aduen, Jairo E. Martinez, Gloria Garcia, Ana Baena, Claudia Guzman, Keith A. Johnson, Reisa A. Sperling, Kaj Blennow, Eric M. Reiman, Francisco Lopera, Yakeel T. Quiroz
Summary: Plasma p-tau217 is a potential predictor of subsequent cognition and pathology in Alzheimer's disease. The study found that carriers of the presenilin-1 E280A gene mutation had higher levels of plasma p-tau217, which was associated with greater amyloid and tau PET pathology burden as well as worse memory performance.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Ana Baena, Yamile Bocanegra, Valeria Torres, Clara Vila-Castelar, Edmarie Guzman-Velez, Joshua T. Fox-Fuller, Jennifer R. Gatchel, Justin Sanchez, Celina F. Pluim, Liliana Ramirez-Gomez, Jairo Martinez, David Pineda, Francisco Lopera, Yakeel T. Quiroz
Summary: This study found that carriers of ADAD reported higher levels of neuroticism compared to non-carriers. Additionally, neuroticism was positively correlated with entorhinal tau levels only in carriers, suggesting a potential relationship between personality traits and AD pathology in preclinical stages.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Antoinette O'Connor, Josef Pannee, Teresa Poole, Charles Arber, Erik Portelius, Imogen J. Swift, Amanda J. Heslegrave, Emily Abel, Nanet Willumsen, Helen Rice, Philip S. J. Weston, Natalie S. Ryan, James M. Polke, Jennifer M. Nicholas, Simon Mead, Selina Wray, Lucia Chavez-Gutierrez, Chris Frost, Kaj Blennow, Henrik Zetterberg, Nick C. Fox
Summary: In this study, differences in amyloid-beta processing between PSEN1 and APP carriers were identified, providing insights into disease pathophysiology and potential implications for therapy development. The analysis of plasma and cell line models demonstrated consistent amyloid-B profiles, with associations found between A beta 42:38, AB42:40, and A beta 38:40 ratios and parental age at onset in the PSEN1 group.
Article
Clinical Neurology
Charles D. Chen, Nelly Joseph-Mathurin, Namita Sinha, Aihong Zhou, Yan Li, Karl Friedrichsen, Austin McCullough, Erin E. Franklin, Russ Hornbeck, Brian Gordon, Vijay Sharma, Carlos Cruchaga, Alison Goate, Celeste Karch, Eric McDade, Chengjie Xiong, Randall J. Bateman, Bernardino Ghetti, John M. Ringman, Jasmeer Chhatwal, Colin L. Masters, Catriona McLean, Tammaryn Lashley, Yi Su, Robert Koeppe, Clifford Jack, William E. Klunk, John C. Morris, Richard J. Perrin, Nigel J. Cairns, Tammie L. S. Benzinger
Summary: The study compared PiB PET imaging signals with postmortem estimation of amyloid-beta burden in ADAD and LOAD patients, showing that PiB PET mainly reflects diffuse plaque burden in ADAD and a mixture of diffuse and cored/compact plaque burden in LOAD. Postmortem stereology identified significantly greater mean amyloid-beta plaque burdens in ADAD versus LOAD across almost all brain regions studied, but standard PiB PET did not recapitulate these findings due to non-trivial plaque burdens in ADAD within common reference regions in PiB PET.
ACTA NEUROPATHOLOGICA
(2021)
Article
Clinical Neurology
Virginia D. Buckles, Chengjie Xiong, Randall J. Bateman, Jason Hassenstab, Ricardo Allegri, Sarah B. Berman, Jasmeer P. Chhatwal, Adrian Danek, Anne M. Fagan, Bernardino Ghetti, Alison Goate, Neill Graff-Radford, Mathias Jucker, Johannes Levin, Daniel S. Marcus, Colin L. Masters, Lena McCue, Eric McDade, Hiroshi Mori, Krista L. Moulder, James M. Noble, Katrina Paumier, Oliver Preische, John M. Ringman, Nick C. Fox, Stephen Salloway, Peter R. Schofield, Ralph Martins, Jonathan Voglein, John C. Morris
Summary: As prevention trials progress with ADAD participants, it is important to understand similarities and differences with sporadic LOAD to ensure generalizability of findings. Cognitive trajectories of ADAD MCs were compared to autopsy-confirmed LOAD individuals, showing differences in rates of decline between the two groups. While both groups showed declining cognitive performance, ADAD MCs declined more rapidly post-symptom onset, indicating common AD pathologies but with some distinct differences.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Stephanie Langella, Francisco Lopera, Ana Baena, Joshua T. Fox-Fuller, Diana Munera, Jairo E. Martinez, Averi Giudicessi, Patrizia Vannini, Bernard J. Hanseeuw, Gad A. Marshall, Yakeel T. Quiroz, Jennifer R. Gatchel
Summary: This study examined the relationship between hippocampal volume and depressive symptoms in preclinical AD patients. The results showed that in carriers of the PSEN1 mutation, smaller hippocampal volume was associated with greater depressive symptoms, while this relationship was not significant in non-carriers.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Victor Montal, Eduard Vilaplana, Jordi Pegueroles, Alexandre Bejanin, Daniel Alcolea, Maria Carmona-Iragui, Jordi Clarimon, Johannes Levin, Carlos Cruchaga, Neill R. Graff-Radford, James M. Noble, Jae-Hong Lee, Ricardo Allegri, Celeste M. Karch, Christoph Laske, Peter R. Schofield, Stephen Salloway, Beau Ances, Tammie Benzinger, Eric McDale, Randall Bateman, Rafael Blesa, Raquel Sanchez-Valle, Alberto Lleo, Juan Fortea
Summary: The study suggests a biphasic trajectory for brain structural changes in early preclinical Alzheimer's disease, with increases in cortical thickness and decreases in cortical diffusivity followed by cortical thinning and cortical diffusivity increases in later stages. The timing of these changes aligns with the start of tau biomarker alterations.
ALZHEIMERS & DEMENTIA
(2021)
Review
Biochemistry & Molecular Biology
Han Na Lee, Mi Suk Jeong, Se Bok Jang
Summary: Amyloid precursor protein (APP) and its homologs play important roles in the nervous system and are overexpressed in cancer cells. Research indicates their involvement in several cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Eric M. Reiman, Jeremy J. Pruzin, Silvia Rios-Romenets, Chris Brown, Margarita Giraldo, Natalia Acosta-Baena, Carlos Tobon, Nan Hu, Yinghua Chen, Valentina Ghisays, Jessica Enos, Dhruman D. Goradia, Wendy Lee, Ji Luo, Michael Malek-Ahmadi, Hillary Protas, Ronald G. Thomas, Kewei Chen, Yi Su, Connie Boker, Diego Mastroeni, Sergio Alvarez, Yakeel T. Quiroz, Jessica B. Langbaum, Kaycee M. Sink, Francisco Lopera, Pierre N. Tariot
Summary: This article reports the availability and process of accessing baseline data from the API ADAD trial, highlighting the importance of sharing data to accelerate progress in the field and explore important questions related to AD prevention.
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
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)
Article
Clinical Neurology
Stephen Zicha, Randall J. Bateman, Leslie M. Shaw, Henrik Zetterberg, Anthony W. Bannon, Wesley A. Horton, Mike Baratta, Hartmuth C. Kolb, Iwona Dobler, Yulia Mordashova, Ziad S. Saad, David L. Raunig, Emmanouil (Manos) Spanakis, Yan Li, Suzanne E. Schindler, Kyle Ferber, Carrie E. Rubel, Robert L. Martone, Christopher J. Weber, Rebecca M. Edelmayer, Emily A. Meyers, James G. Bollinger, Erin G. Rosenbaugh, William Z. Potter
Summary: This study evaluated the performance of six plasma A beta assays in predicting amyloid positivity compared to age and APOE genotype. The results showed that three of the assays significantly improved the prediction accuracy, and plasma A beta 42/40 predicted amyloid PET status better than A beta 42 or A beta 40 alone.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Sarah M. Hartz, Jessica Mozersky, Suzanne E. Schindler, Erin Linnenbringer, Junwei Wang, Brian A. Gordon, Cyrus A. Raji, Krista L. Moulder, Tim West, Tammie L. S. Benzinger, Carlos Cruchaga, Jason J. Hassenstab, Laura J. Bierut, Chengjie Xiong, John C. Morris
Summary: In this study, the authors developed and validated an adaptive tool to compute the absolute risks of Alzheimer's disease (AD) dementia, using demographic factors, clinical and cognitive variables, and biomarkers. This approach provides improved accuracy and communication of AD risk among cognitively unimpaired older adults.
ALZHEIMERS & DEMENTIA
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Anne M. Smith, Nancy A. Obuchowski, Norman L. Foster, Gregory Klein, P. David Mozley, Adriaan A. Lammertsma, Richard L. Wahl, John J. Sunderland, Jean-Luc Vanderheyden, Tammie L. S. Benzinger, Paul E. Kinahan, Dean F. Wong, Eric S. Perlman, Satoshi Minoshima, Dawn Matthews
Summary: Standardized approach in acquiring amyloid PET images increases their value as disease and drug response biomarkers. The Quantitative Imaging Biomarkers Alliance amyloid PET biomarker committee developed and validated a profile to characterize and reduce the variability of SUVRs, increasing statistical power for these assessments.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Clinical Neurology
Jessica Nicosia, Andrew J. Aschenbrenner, David A. Balota, Martin J. Sliwinski, Marisol Tahan, Sarah Adams, Sarah S. Stout, Hannah Wilks, Brian A. Gordon, Tammie L. S. Benzinger, Anne M. Fagan, Chengjie Xiong, Randall J. Bateman, John C. Morris, Jason Hassenstab
Summary: This study confirms the reliability and validity of the ARC smartphone application as a feasible tool for assessing cognitive changes associated with early stages of Alzheimer's disease in older adults. The ARC tasks are reliable and correlated with conventional cognitive measures and AD biomarker burden. The intensive 7-day cycle of ARC testing was feasible and well tolerated by older adult participants, receiving favorable ratings.
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
(2023)
Article
Clinical Neurology
Pratishtha Chatterjee, Lisa Vermunt, Brian A. Gordon, Steve Pedrini, Lynn Boonkamp, Nicola J. Armstrong, Chengjie Xiong, Abhay K. Singh, Yan Li, Hamid R. Sohrabi, Kevin Taddei, Mark Molloy, Tammie L. S. Benzinger, John C. Morris, Celeste Karch, Sarah Berman, Jasmeer Chhatwal, Carlos Cruchaga, Neill R. Graff-Radford, Gregory S. Day, Martin Farlow, Nick Fox, Alison Goate, Jason Hassenstab, Jae-Hong Lee, Johannes Levin, Eric McDade, Hiroshi Mori, Richard Perrin, Raquel Sanchez-Valle, Peter R. Schofield, Allan Levey, Mathias Jucker, Colin L. Masters, Anne M. Fagan, Randall J. Bateman, Ralph N. Martins, Charlotte Teunissen
Summary: This study found that plasma GFAP levels increase a decade before symptom onset in AD and are associated with Aβ load, neurodegeneration, and cognitive decline.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Chengjie Xiong, Lena M. McCue, Virginia Buckles, Elizabeth Grant, Folasade Agboola, Dean Coble, Randall J. Bateman, Anne M. Fagan, Tammie L. S. Benzinger, Jason Hassenstab, Suzanne E. Schindler, Eric McDade, Krista Moulder, Brian A. Gordon, Carlos Cruchaga, Gregory S. Day, Takeshi Ikeuchi, Kazushi Suzuki, Ricardo F. Allegri, Jonathan Voeglein, Johannes Levin, John C. Morris
Summary: This study compared biomarkers of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD). The results showed that at baseline, ADAD mutation carriers (MCs) had lower CSF A beta 42 levels and higher levels of total and phosphorylated tau-181, and PiB uptake compared to LOAD participants with a positive family history (FH+). Longitudinally, MCs had a similar increase in PiB uptake to FH+, but a much faster decline in hippocampal volume, and were the only group showing cognitive decline.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Julie K. Wisch, Omar H. Butt, Brian A. Gordon, Suzanne E. Schindler, Anne M. Fagan, Rachel L. Henson, Chengran Yang, Anna H. Boerwinkle, Tammie L. S. Benzinger, David M. Holtzman, John C. Morris, Carlos Cruchaga, Beau M. Ances
Summary: Heterogeneity in progression to Alzheimer's disease poses challenges for prognosis and clinical trials. By analyzing CSF proteomics, researchers identified early differences in biomarkers and assessed patterns of preclinical AD development. These findings have important implications for participant selection and potential therapies in clinical trials.
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
Clinical Neurology
F. Rahmani, S. Jindal, C. A. Raji, W. Wang, A. Nazeri, G. G. Perez-Carrillo, M. M. Miller-Thomas, P. Graner, B. Marechal, A. Shah, M. Zimmermann, C. D. Chen, S. Keefe, P. LaMontagne, T. L. S. Benzinger
Summary: Auto volumetric analysis of brain MRI provides quantitative assessment of brain atrophy. In this study, the performance of AI-Rad Companion brain MRI software was compared to FreeSurfer pipeline. The results showed strong correlation, moderate consistency, and poor agreement in volume measurements between the two tools. The AI-Rad Companion tool had high specificity and sensitivity in detecting volumetric abnormalities compared to the FreeSurfer pipeline. There was no difference in the compatibility of radiologic and clinical impressions between the two tools.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Erik C. B. Johnson, Shijia Bian, Rafi U. Haque, E. Kathleen Carter, Caroline M. Watson, Brian A. Gordon, Lingyan Ping, Duc M. Duong, Michael P. Epstein, Eric McDade, Nicolas R. Barthelemy, Celeste M. Karch, Chengjie Xiong, Carlos Cruchaga, Richard J. Perrin, Aliza P. Wingo, Thomas S. Wingo, Jasmeer P. Chhatwal, Gregory S. Day, James M. Noble, Sarah B. Berman, Ralph Martins, Neill R. Graff-Radford, Peter R. Schofield, Takeshi Ikeuchi, Hiroshi Mori, Johannes Levin, Martin Farlow, James J. Lah, Christian Haass, Mathias Jucker, John C. Morris, Tammie L. S. Benzinger, Blaine R. Roberts, Randall J. Bateman, Anne M. Fagan, Nicholas T. Seyfried, Allan Levey
Summary: Alzheimer's disease pathology, characterized by aggregation of Aβ peptide into plaques and tau protein into neurofibrillary tangles, develops years before cognitive symptoms. By analyzing cerebrospinal fluid proteomics in individuals with autosomal dominant AD, researchers identified protein changes associated with Aβ plaques and their temporal evolution over six decades. These proteomic measurements were able to differentiate mutation carriers from noncarriers before symptom onset better than traditional Aβ and tau measures. Understanding the multifaceted landscape of AD pathology and its progression is crucial for developing precise therapeutic interventions and biomarkers.
Article
Cell Biology
Nicolas R. Barthelemy, Benjamin Saef, Yan Li, Brian A. Gordon, Yingxin He, Kanta Horie, Erik Stomrud, Gemma Salvado, Shorena Janelidze, Chihiro Sato, Vitaliy Ovod, Rachel L. Henson, Anne M. Fagan, Tammie L. S. Benzinger, Chengjie Xiong, John C. Morris, Oskar Hansson, Randall J. Bateman, Suzanne E. Schindler
Summary: CSF tau phosphorylation at T217 and T205 sites is a better marker for Alzheimer's disease pathology than current tests.
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)
Article
Clinical Neurology
Julie K. Wisch, Brian A. Gordon, Anna H. Boerwinkle, Patrick H. Luckett, James G. Bollinger, Vitaliy Ovod, Yan Li, Rachel L. Henson, Tim West, Mathew R. Meyer, Kristopher M. Kirmess, Tammie L. S. Benzinger, Anne M. Fagan, John C. Morris, Randall J. Bateman, Beau M. Ances, Suzanne E. Schindler
Summary: This study investigated whether cerebrospinal fluid (CSF) and plasma levels of amyloid beta (A13)42/A1340 could predict continuous values for amyloid positron emission tomography (PET) burden. The results showed that CSF A1342/A1340 predicted a wider range of amyloid plaque burden and may be useful in staging Alzheimer's disease (AD).
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)