Article
Biochemistry & Molecular Biology
Michela Marcatti, Anna Fracassi, Mauro Montalbano, Chandramouli Natarajan, Balaji Krishnan, Rakez Kayed, Giulio Taglialatela
Summary: This study demonstrates that Tau oligomers become the main synaptotoxic species in late-stage Alzheimer's disease (AD), supporting the hypothesis that targeting Tau oligomers may be the most effective therapeutic approach for clinically manifest AD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Moeko Noguchi-Shinohara, Kenjiro Ono
Summary: LBD is a disease characterized by the accumulation of Lewy bodies composed of alpha-synuclein (aSyn). This review discusses the co-aggregation of aSyn, amyloid-beta (A beta), and tau proteins, as well as advancements in imaging and fluid biomarkers for detecting these pathologies. It also summarizes the current clinical trials of disease-modifying therapies targeting aSyn.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Elijah Mak, Nicolas Nicastro, Maura Malpetti, George Savulich, Ajenthan Surendranathan, Negin Holland, Luca Passamonti, P. Simon Jones, Stephen F. Carter, Li Su, Young T. Hong, Tim D. Fryer, Guy B. Williams, Franklin Aigbirhio, James B. Rowe, John T. O'Brien
Summary: The study examined the distribution of tau burden in patients with DLB and AD, revealing a lower tau deposition in DLB patients compared to AD patients. The findings suggest that tau may interact synergistically with other pathologic processes to aggravate disease severity in DLB, as indicated by its associations with cognitive impairment.
NEUROBIOLOGY OF AGING
(2021)
Article
Clinical Neurology
Julia Schumacher, Jeffrey L. Gunter, Scott A. Przybelski, David T. Jones, Jonathan Graff-Radford, Rodolfo Savica, Christopher G. Schwarz, Matthew L. Senjem, Clifford R. Jack, Val J. Lowe, David S. Knopman, Julie A. Fields, Walter K. Kremers, Ronald C. Petersen, Neill R. Graff-Radford, Tanis J. Ferman, Bradley F. Boeve, Alan J. Thomas, John-Paul Taylor, Kejal Kantarci
Summary: The presence of concurrent Alzheimer's disease pathology in patients with DLB is associated with more severe loss of default mode network connectivity. Additionally, higher functional connectivity between brain regions is related to higher tau pathology levels in cognitively normal, Alzheimer's disease, and DLB patients.
Article
Biochemistry & Molecular Biology
Melina J. Lim, Suelen L. Boschen, Aishe Kurti, Monica Castanedes Casey, Virginia R. Phillips, John D. Fryer, Dennis Dickson, Karen R. Jansen-West, Leonard Petrucelli, Marion Delenclos, Pamela J. Mclean
Summary: The study aimed to evaluate whether the overexpression of alpha syn and tau in mice resulted in pathological and behavioral phenotypes resembling Lewy body dementia (LBD). The findings showed that the overexpression of alpha syn in hTau and APP/PS1 mice, as well as the overexpression of tau in hThy1-alpha syn mice, did not recapitulate the behavioral and neuropathological phenotypes observed in LBD.
Article
Neurosciences
Sonja Fixemer, Corrado Ameli, Gael Hammer, Luis Salamanca, Oihane Uriarte Huarte, Chantal Schwartz, Jean-Jacques Gerardy, Naguib Mechawar, Alexander Skupin, Michel Mittelbronn, David S. Bouvier
Summary: Cellular alterations in the hippocampus lead to memory decline, a shared symptom in AD and DLB patients. The subregional deterioration patterns differ between AD and DLB, with CA1 being more severely affected in AD. Microglial activation may play a role in selective volume loss in the hippocampus.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Xiaobing Huang, Changliang Wang, Liang Chen, Tianjiao Zhang, Ka Lai Leung, Garry Wong
Summary: The study found that the co-expression of A beta and alpha-synuclein in the brains of patients with Lewy body dementia may exacerbate the pathogenic process. The experimental results showed that co-expression of A beta and alpha-syn (A53T) in C. elegans further aggravated movement, egg laying, signaling deficits, and dopaminergic neuron damage. These findings suggest a potential mechanism by which A beta may enhance alpha-syn pathogenesis in Lewy body dementia.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Geriatrics & Gerontology
Jiajun Han, Yaohua Fan, Peipei Wu, Zifeng Huang, Xinrong Li, Lijun Zhao, Yichun Ji, Meiling Zhu
Summary: Parkinson's disease dementia is a common complication of Parkinson's disease that seriously affects patients' health and quality of life. The complex interplay of iron, alpha-synuclein, tau, beta-amyloid, and oxidative stress plays a pivotal role in the mechanism underlying PDD, leading to neuronal protein accumulation, neuroinflammation, and cell death. GSK3 beta is identified as a potential target for the prevention and treatment of PDD due to its central role in regulating the vicious cycle of molecular interactions.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Neurosciences
Nolwazi Z. Gcwensa, Dreson L. Russell, Rita M. Cowell, Laura A. Volpicelli-Daley
Summary: Parkinson's disease is a progressive neurodegenerative disease with no treatment to slow its progression. Evidence suggests that synaptic impairments may precede neuronal cell loss, highlighting the need for novel therapeutics targeting the synapse. Genetic studies implicate several genes in synaptic dysfunction in PD, and future studies should explore the roles of implicated genes across multiple neuron types and circuits.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Masahiro Kawahara, Midori Kato-Negishi, Ken-ichiro Tanaka
Summary: Prion diseases are progressive and transmissive neurodegenerative diseases, where the conversion of normal cellular prion protein (PrP(C)) into abnormal pathogenic prion protein (PrPSc) is critical. PrP(C) has the ability to bind to various neurometals and plays essential roles in maintaining the homeostasis of these neurometals at the synapse, which are critical determinants of the conformational change and toxicity of PrP(C).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Manuel Moreno-Valladares, Veronica Moncho-Amor, Iraide Bernal-Simon, Enaut Agirre-Iturrioz, Maria Alvarez-Satta, Ander Matheu
Summary: This case report highlights a complex interplay between norovirus infection, alpha-synuclein synthesis in the gastrointestinal mucosa, and Lewy pathology in the central nervous system in an older woman with unspecific symptoms. The presence of alpha-synuclein deposits and Lewy pathology support Braak's hypothesis about the pathogenic mechanisms underlying synucleinopathies, providing valuable insights into the understanding of these disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
Gregory D. Scott, Moriah R. Arnold, Thomas G. Beach, Christopher H. Gibbons, Anumantha G. Kanthasamy, Russell M. Lebovitz, Afina W. Lemstra, Leslie M. Shaw, Charlotte E. Teunissen, Henrik Zetterberg, Angela S. Taylor, Todd C. Graham, Bradley F. Boeve, Stephen N. Gomperts, Neill R. Graff-Radford, Charbel Moussa, Kathleen L. Poston, Liana S. Rosenthal, Marwan N. Sabbagh, Ryan R. Walsh, Miriam T. Weber, Melissa J. Armstrong, Jee A. Bang, Andrea C. Bozoki, Kimiko Domoto-Reilly, John E. Duda, Jori E. Fleisher, Douglas R. Galasko, James E. Galvin, Jennifer G. Goldman, Samantha K. Holden, Lawrence S. Honig, Daniel E. Huddleston, James B. Leverenz, Irene Litvan, Carol A. Manning, Karen S. Marder, Alexander Y. Pantelyat, Victoria S. Pelak, Douglas W. Scharre, Sharon J. Sha, Holly A. Shill, Zoltan Mari, Joseph F. Quinn, David J. Irwin
Summary: The LBDA Biofluid/Tissue Biomarker Symposium, held by the Lewy Body Dementia Association, presented advancements in biomarkers for Lewy body dementia (LBD) and attracted over 200 scientists and physicians from various institutions. The methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology, as well as novel biomarkers, were discussed.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Erika B. Villanueva, Emilie Tresse, Yawei Liu, Joao N. Duarte, Gisela Jimenez-Duran, Patrick Ejlerskov, Oliver Kretz, Desiree Loreth, Tobias Goldmann, Marco Prinz, Shohreh Issazadeh-Navikas
Summary: In sporadic PDD, targeting alpha-syn alone may not be sufficient to alleviate the disease. Targeting specific aspects of neuroinflammation, such as aberrant neuronal TNF-alpha/TNFR1 or IFN-beta/IFNAR signaling, may attenuate the disease.
ANNALS OF NEUROLOGY
(2021)
Article
Neurosciences
Per Borghammer, Jacob Horsager, Katrine Andersen, Nathalie Van den Berge, Anna Raunio, Shigeo Murayama, Laura Parkkinen, Liisa Myllykangas
Summary: The aggregation of alpha-synuclein into inclusion bodies, known as Lewy pathology, is a key feature of Parkinson's disease and Dementia with Lewy bodies. Post mortem studies have shown that Lewy pathology follows two main distribution patterns in the brain, with some patients having pathogenic alpha-synuclein originating in the enteric nervous system and others originating inside the central nervous system.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Geriatrics & Gerontology
Stacy L. Andersen, Mengtian Du, Stephanie Cosentino, Nicole Schupf, Andrea L. Rosso, Thomas T. Perls, Paola Sebastiani
Summary: Individuals from families with familial longevity demonstrate better cognitive performance and slower rates of cognitive aging, particularly in processing speed, memory, and integration abilities. They may serve as a valuable cohort for studying resilience to cognitive aging.
Article
Clinical Neurology
Ashlyn M. Bulas, Lihua Li, Raj G. Kumar, Madhu Mazumdar, Andrea L. Rosso, Ada O. Youk, Kristen Dams-O'Connor
Summary: This study found that individuals who sustained a traumatic brain injury (TBI) had significantly higher odds of experiencing depression in the year prior to the injury compared to matched controls. However, there were no significant differences in preexisting health conditions or poor health behaviors between TBI cases and controls.
JOURNAL OF HEAD TRAUMA REHABILITATION
(2022)
Article
Geriatrics & Gerontology
Andrea L. Rosso, Zachary A. Marcum, Xiaonan Zhu, Nicolaas Bohnen, Caterina Rosano
Summary: Anticholinergic medication use is associated with an increased risk of falls, while higher dopaminergic signaling may provide protection against this.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Geriatrics & Gerontology
Qu Tian, Rebecca Ehrenkranz, Andrea L. Rosso, Nancy W. Glynn, Lana M. Chahine, James Hengenius, Xiaonan Zhu, Caterina Rosano
Summary: MPS may lead to a decline in SEL, and striatal atrophy may be associated with energy decline, but cannot explain the association with MPS.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Geriatrics & Gerontology
Pamela M. Dunlap, Andrea L. Rosso, Xiaonan Zhu, Brooke N. Klatt, Jennifer S. Brach
Summary: The study aimed to identify the association between mobility determinants and life space in older adults. The results showed that age, lower extremity power, gait efficacy, and energy cost of walking were associated with life space.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Clinical Neurology
James B. Hengenius, Nicolaas Bohnen, Andrea Rosso, Theodore J. Huppert, Caterina Rosano
Summary: This study found that MPS in older adults may be associated with lower FC in the executive network, particularly more pronounced in patients with higher WMH burden.
JOURNAL OF NEUROIMAGING
(2022)
Article
Geriatrics & Gerontology
Kyle D. Moored, Andrea L. Rosso, Theresa Gmelin, Yujia (Susanna) Qiao, Michelle C. Carlson, Peggy M. Cawthon, Jane A. Cauley, Nancy W. Glynn
Summary: The study found that higher levels of physical and mental fatigability are associated with lower life-space mobility in older men, even after adjusting for health and lifestyle factors. This suggests that fatigability is linked with real-world mobility independent of physical health, with potential separate physical and cognitive mechanisms driving this association.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Neurosciences
Wendy M. Troxel, Ann Haas, Tamara Dubowitz, Bonnie Ghosh-Dastidar, Meryl A. Butters, Tiffany L. Gary-Webb, Andrea M. Weinstein, Andrea L. Rosso
Summary: This study examined the impact of sleep problems on cognitive function in a predominantly African American sample. The results showed that higher sleep efficiency and less wakefulness after sleep onset were associated with better attention, executive function, and visuospatial ability. Additionally, improvements in sleep efficiency were linked to better executive function, language, immediate recall, and visuospatial ability, while increases in wakefulness after sleep onset were associated with poorer attention, executive function, and visuospatial ability.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Geriatrics & Gerontology
Roee Holtzer, Xiaonan Zhu, Andrea L. Rosso, Caterina Rosano
Summary: Higher baseline cognitive reserve is protective against the development of mobility impairment in older adults.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Geriatrics & Gerontology
Fengyan Tang, Ke Li, Andrea L. Rosso, Yanping Jiang, Mengting Li
Summary: This study examined the associations of neighborhood segregation and socioeconomic status (NSES) with cognitive functioning among older Chinese immigrants. The findings suggest that living in high-NSES neighborhoods is associated with slower cognitive decline, and neighborhood segregation does not directly affect cognitive functioning but can enhance the protective effect of high NSES on cognitive decline.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Public, Environmental & Occupational Health
Sara L. Godina, Andrea L. Rosso, Jana A. Hirsch, Lilah M. Besser, Gina S. Lovasi, Geoffrey H. Donovan, Parveen K. Garg, Jonathan M. Platt, Annette L. Fitzpatrick, Oscar L. Lopez, Michelle C. Carlson, Yvonne L. Michael
Summary: This study examines the association between greenspace measures and clinically adjudicated dementia status. The results show that overall percent greenspace and forest have no significant impact on the risk of mild cognitive impairment or dementia, while forest greenspace is inversely associated with the risk of mild cognitive impairment and greenspace diversity is inversely associated with the hazard of incident dementia. The study suggests the need for improved measurement of greenspace types and diversity to better understand the association with cognition.
Article
Geriatrics & Gerontology
Cristina Udina, Stella Avtzi, Miriam Mota-Foix, Andrea L. Rosso, Joan Ars, Lisa Kobayashi Frisk, Clara Gregori-Pla, Turgut Durduran, Marco Inzitari
Summary: Older adults with mild cognitive impairment (MCI) exhibit differential prefrontal hemodynamic patterns compared to their counterparts with normal cognition (NC) during dual-task performance, possibly as a response to increasing attentional demand.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Public, Environmental & Occupational Health
Wendy M. Troxel, Jaime Madrigano, Ann C. Haas, Tamara Dubowitz, Andrea L. Rosso, Aric A. Prather, Madhumita Ghosh-Dastidar, Andrea M. Weinstein, Meryl A. Butters, Albert Presto, Tiffany L. Gary-Webb
Summary: Disadvantageous neighborhood conditions and discrimination contribute to health disparities among African Americans. This study examined their associations with leukocyte telomere length in a predominantly African American cohort. Results showed that less walkable neighborhoods were associated with shorter telomeres, and higher air pollution (PM2.5) was associated with shorter telomeres among those experiencing more discrimination. These findings underscore the importance of understanding the intersecting influences of historical and contemporary systemic racism on accelerated aging.
JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES
(2023)
Article
Public, Environmental & Occupational Health
Andrea L. Rosso, Wendy M. Troxel, Tiffany L. Gary-Webb, Andrea M. Weinstein, Meryl A. Butters, Alina Palimaru, Bonnie Ghosh-Dastidar, La'Vette Wagner, Alvin Nugroho, Gerald Hunter, Jennifer Parker, Tamara Dubowitz
Summary: The Think PHRESH study aims to examine the impact of race and societal factors on the risk of Alzheimer's disease and related dementias in Black Americans. The study will collect data through surveys, physiological measurements, and in-depth interviews to understand the effects of social inequality on cognitive health.
Review
Geriatrics & Gerontology
Anisha Suri, Jessie VanSwearingen, Pamela Dunlap, Mark S. Redfern, Andrea L. Rosso, Ervin Sejdic
Summary: This review article summarizes the common mobility measures extracted from wearable sensors, as well as the studies assessing the associations between facilitators and barriers to community mobility and mobility measures from sensor technology. The findings suggest that cognition and psychosocial influences are important facilitators or barriers to community mobility, while fewer studies have considered the influence of external environmental factors. Understanding these factors can inform interventions using wearable technology to delay mobility-related disability and improve participation in older adults.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
