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
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
Diego Sepulveda-Falla, Justin S. Sanchez, Maria Camila Almeida, Daniela Boassa, Juliana Acosta-Uribe, Clara Vila-Castelar, Liliana Ramirez-Gomez, Ana Baena, David Aguillon, Nelson David Villalba-Moreno, Jessica Lisa Littau, Andres Villegas, Thomas G. Beach, Charles L. White, Mark Ellisman, Susanne Krasemann, Markus Glatzel, Keith A. Johnson, Reisa A. Sperling, Eric M. Reiman, Joseph F. Arboleda-Velasquez, Kenneth S. Kosik, Francisco Lopera, Yakeel T. Quiroz
Summary: This study presents PET imaging and postmortem findings of an ADAD PSEN1 E280A carrier with the APOE3 Christchurch (APOE3ch) variant, who remained symptom-free for nearly three decades past the expected age of onset. It revealed a unique anatomical pattern of tau pathology, with atypical accumulation in vivo and distinct regional distribution in the postmortem analysis. The frontal cortex and hippocampus, less affected by tau pathology, displayed specific cell types and higher APOE expression, while the occipital cortex, the only region with cerebral amyloid angiopathy (CAA), showed chronic inflammation and lower APOE expression. This suggests that the Christchurch variant may impact tau pathology distribution and modulate the clinical presentation of ADAD.
ACTA NEUROPATHOLOGICA
(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
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
Angelica Zuno-Reyes, Esmeralda Matute, Karin Ernstrom, Mellissa Withers, Yaneth Rodriguez-Agudelo, Rema Raman, John M. Ringman
Summary: This study aimed to investigate the attitudes towards participation in clinical trials among ADAD risk family members in Mexico and the United States. It found that participants living in Mexico, especially those in rural areas, with or planning to have children, and not attending school, were more willing to participate. The main motivation for participation was to help future generations, while the main reasons for refusal were unwillingness to undergo genetic testing and concerns about side effects.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Clinical Neurology
Charlotte Johansson, Steinunn Thordardottir, Jose Laffita-Mesa, Elena Rodriguez-Vieitez, Henrik Zetterberg, Kaj Blennow, Caroline Graff
Summary: The study describes plasma biomarkers in a Swedish cohort of patients with monogenic Alzheimer's disease. Plasma GFAP increases before P-tau181 and NfL, indicating that it reflects early Alzheimer's disease pathology. Plasma biomarkers may be non-invasive tools to detect Alzheimer's disease-related abnormalities. However, further validation is needed.
Article
Clinical Neurology
Dorothee Schoemaker, Maria Clara Zanon Zotin, Kewei Chen, Kay C. Igwe, Clara Vila-Castelar, Jairo Martinez, Ana Baena, Joshua T. Fox-Fuller, Francisco Lopera, Eric M. Reiman, Adam M. Brickman, Yakeel T. Quiroz
Summary: This study found that white matter abnormalities increase in individuals with early-onset autosomal dominant Alzheimer's disease, beginning to increase before clinical symptom onset, which is an independent determinant of cognitive performance.
ALZHEIMERS RESEARCH & THERAPY
(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
Patrick H. Luckett, Austin McCullough, Brian A. Gordon, Jeremy Strain, Shaney Flores, Aylin Dincer, John McCarthy, Todd Kuffner, Ari Stern, Karin L. Meeker, 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 Klunk, Robert Koeppe, Hwamee Oh, Yi Su, Michael Weiner, Qing Wang, Laura Swisher, Dan 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: Machine learning models were used to discover novel disease trajectories for autosomal dominant Alzheimer's disease, with results suggesting a sigmoidal trajectory for amyloid, a biphasic response for metabolism, and a gradual decrease in volume, with disease progression primarily in subcortical, middle frontal, and posterior parietal regions.
ALZHEIMERS & DEMENTIA
(2021)
Article
Clinical Neurology
Christopher J. Becker, Steven G. Heeringa, Wen Chang, Emily M. Briceno, Roshanak Mehdipanah, Deborah A. Levine, Kenneth M. Langa, Xavier F. Gonzales, Nelda Garcia, Ruth Longoria, Mellanie Springer, Darin B. Zahuranec, Lewis B. Morgenstern
Summary: The study found that there is an association between history of stroke and cognitive impairment in underrepresented ethnic groups. Regardless of ethnicity, increased age and lower educational attainment are also associated with cognitive impairment. However, the impact of stroke on cognition is greater in non-Hispanic Whites.
Article
Clinical Neurology
Breton M. Asken, Wei-En Wang, Karen Mcfarland, Franchesca Arias, Jacob Fiala, Idaly Velez-Uribe, Robin P. Mayrand, Luana Okino Sawada, Christian Freytes, Michael Adeyosoye, Michael Marsiske, Monica Rosselli, Warren W. Barker, Rosie Curiel Cid, David A. Loewenstein, Steven T. Dekosky, Melissa J. Armstrong, Glenn E. Smith, Malek Adjouadi, David E. Vaillancourt, Ranjan Duara
Summary: This study highlights the importance of ethnic diversity in Alzheimer's disease research and the potential role of plasma p-tau181 as a biomarker for early diagnosis. The findings suggest that Hispanic ethnicity may be related to a greater likelihood of non-Alzheimer's contributions to memory loss.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Clara Vila-Castelar, Yinghua Chen, Stephanie Langella, Francisco Lopera, Henrik Zetterberg, Oskar Hansson, Jeffrey L. Dage, Shorena Janelidzde, Yi Su, Kewei Chen, Celina Pluim McDowell, Jairo E. Martinez, Liliana Ramirez-Gomez, Gloria Garcia, David Aguillon, Ana Baena, Margarita Giraldo-Chica, Hillary D. Protas, Valentina Ghisays, Silvia Rios-Romenets, Pierre N. Tariot, Kaj Blennow, Eric M. Reiman, Yakeel T. Quiroz
Summary: This study found that female carriers of Presenilin-1 E280A mutation had higher levels of plasma phosphorylated tau at threonine 217 (P-tau217) than male carriers when their cognitive abilities were intact, but as the disease progressed, female carriers showed a greater increase in plasma neurofilament light (NfL) levels than male carriers. However, among non-carriers, there were no significant differences in sex and plasma biomarkers.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Natalia Acosta-Baena, Carlos M. Lopera-Gomez, Mario C. Jaramillo-Elorza, Lina Velilla-Jimenez, Carlos Andres Villegas-Lanau, Diego Sepulveda-Falla, Mauricio Arcos-Burgos, Francisco Lopera
Summary: This study evaluated the association between depressive symptoms and age of onset of cognitive decline in autosomal dominant Alzheimer's disease (AD), finding that AD patients with depressive symptoms develop dementia faster. Not having a stable partner accelerated the onset of cognitive decline. Controlled hypothyroidism delayed the onset of depressive symptoms, dementia, and death.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Geriatrics & Gerontology
Madelyn Malvitz, Darin B. B. Zahuranec, Wen Chang, Steven G. G. Heeringa, Emily M. M. Briceno, Roshanak Mehdipanah, Xavier F. F. Gonzales, Deborah A. A. Levine, Kenneth M. M. Langa, Nelda Garcia, Lewis B. B. Morgenstern
Summary: This study investigated the driving status among older Latinx and non-Hispanic White individuals with cognitive impairment. The majority of participants were still driving, which is a concern for caregivers. Factors such as language preference and daily living activities were associated with driving status, but no significant ethnic differences were found.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2023)