Article
Geriatrics & Gerontology
Violetta N. Pivtoraiko, Tamara Racic, Eric E. Abrahamson, Victor L. Villemagne, Benjamin L. Handen, Ira T. Lott, Elizabeth Head, Milos D. Ikonomovic
Summary: Individuals with Down syndrome (DS) have a different molecular profile of A beta forms compared to late-onset Alzheimer's disease (AD) cases, with a higher preponderance of pyroglutamate-modified A beta NpE3-40 and unmodified A beta 40 forms. Despite greater vascular amyloidosis in DS cases, cortical H-3-PiB binding does not distinguish between diagnostic groups at an advanced level of amyloid plaque pathology.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Review
Neurosciences
Blandine Ponroy Bally, Keith K. Murai
Summary: Down Syndrome (DS) is the most common genetic cause of intellectual disability, traditionally focusing on neurons, but recent studies have highlighted the role of non-neuronal cells, especially astrocytes, in DS. Understanding the impact of trisomy 21 on astrocytes in DS may be crucial in determining specific brain alterations and neurological phenotypes in DS.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Antonella Tramutola, Simona Lanzillotta, Giuseppe Aceto, Sara Pagnotta, Gabriele Ruffolo, Pierangelo Cifelli, Federico Marini, Cristian Ripoli, Eleonora Palma, Claudio Grassi, Fabio Di Domenico, Marzia Perluigi, Eugenio Barone
Summary: Down syndrome (DS) is associated with Alzheimer's disease (AD) and brain insulin resistance. The KYCCSRK peptide has shown potential for improving insulin signaling in DS and reducing AD-like neuropathology in mice.
Article
Neurosciences
Sigan L. Hartley, Victoria Fleming, Emily K. Schworer, Jamie Peven, Benjamin L. Handen, Sharon Krinsky-McHale, Christy Hom, Laisze Lee, Dana L. Tudorascu, Charles Laymon, Davneet Minhas, Weiquan Luo, Annie Cohen, Shahid Zaman, Beau M. Ances, Mark Mapstone, Elizabeth Head, Florence Lai, H. Diana Rosas, William Klunk, Bradley Christian
Summary: This study aimed to investigate whether premorbid intellectual disability level was associated with the variability in age-trajectories of Alzheimer's disease biomarkers and cognitive impairments. The results showed no significant effect of premorbid intellectual disability level on the trajectories of Alzheimer's disease biomarkers and cognitive outcomes.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Luciana Mascarenhas Fonseca, Guilherme Prado Mattar, Glenda Guerra Haddad, Ekaterina Burduli, Sterling M. McPherson, Laura Maria de Figueiredo Ferreira Guilhoto, Monica Sanches Yassuda, Geraldo Filho Busatto, Cassio Machado de Campos Bottino, Marcelo Queiroz Hoexter, Naomi Sage Chaytor
Summary: Research investigated neuropsychiatric symptoms (NPS) and caregiver distress in adults with Down syndrome (DS), finding that NPS are common and severe in DS and AD patients, contributing to caregiver distress. Symptoms of apathy, nighttime behavior disturbances, and appetite abnormalities had the greatest impact on caregiver distress.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Matthew D. Zammit, Dana L. Tudorascu, Charles M. Laymon, Sigan L. Hartley, Shahid H. Zaman, Beau M. Ances, Sterling C. Johnson, Charles K. Stone, Chester A. Mathis, William E. Klunk, Ann D. Cohen, Benjamin L. Handen, Bradley T. Christian
Summary: Longitudinal imaging studies in adults with Down syndrome identified A beta accumulation trajectories and early accumulation sites; A beta(-) group, A beta converters, and A beta (+) group showed differences in A beta(L) change; Model images and A beta(L) change values can better identify subthreshold A beta accumulation in DS.
Review
Nutrition & Dietetics
Carmen Martinez-Cue, Renata Bartesaghi
Summary: Down syndrome (DS) is a genetic disorder caused by the triplication of chromosome 21, resulting in intellectual disability starting in utero and continuing through infancy, with associated impairments in neurogenesis and connectivity that may lead to early-onset Alzheimer's disease. Current research focuses on using DS mouse models to discover potential pharmacotherapies, with fatty acids emerging as a promising treatment option for DS-related cognitive deficits and neurodevelopmental impairments. This suggests a need for further exploration of the potential benefits of fatty acids for individuals with DS.
Article
Immunology
Lauren E. Oberlin, Kirk I. Erickson, Rachel Mackey, William E. Klunk, Howard Aizenstein, Brian J. Lopresti, Lewis H. Kuller, Oscar L. Lopez, Beth E. Snitz
Summary: In oldest-old cognitively unimpaired adults, peripheral inflammatory biomarkers are associated with and predictive of the progression of Aβ deposition, specifically among those with biomarker evidence of preclinical AD at baseline. This suggests that chronic, low-level systemic inflammation may exacerbate the deposition of Aβ pathology and increase the risk of clinically significant cognitive impairment.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Psychiatry
Mina Idris, Fedal Saini, Sarah E. Pape, R. Asaad Baksh, Marie-Stephanie Cahart, Andre Strydom
Summary: This study investigated the impact of CMDs on cognitive ability and clinical signs of Alzheimer's disease in individuals with Down syndrome. The results suggest that a diagnosis of CMDs does not have a significant negative effect on long-term cognitive or behavioral outcomes in these individuals.
Review
Clinical Neurology
Yara Abukhaled, Kenana Hatab, Mohammad Awadhalla, Hamdan Hamdan
Summary: Down syndrome (DS), trisomy 21, is the most common genetic cause of intellectual disability. It results from three copies of human chromosome 21 (HC21), leading to altered transcription of genes on HC21 and a wide range of symptoms affecting all organ systems. Intellectual disability is a debilitating aspect of DS, and there is a lack of unified understanding and management of its underlying mechanisms. This literature review explores neuronal over-inhibition, abnormal morphology, and other genetic factors contributing to the development of intellectual disability in DS patients, with a focus on potential therapeutic approaches to improve their quality of life.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Jong-Chan Park, Keum Sim Jung, Jiyeong Kim, Ji Sung Jang, Sunghoon Kwon, Min Soo Byun, Dahyun Yi, Gihwan Byeon, Gijung Jung, Yu Kyeong Kim, Dong Young Lee, Sun-Ho Han, Inhee Mook-Jung
Summary: The QPLEX (TM) Alz plus assay kit shows promise as a blood marker for predicting cerebral amyloid deposition, achieving an accuracy of 81.5% with 89.1% area under curve (AUC), 80.0% sensitivity, and 83.0% specificity. However, further independent validation is necessary.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Clinical Neurology
Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone
Summary: The study found that nEVs isolated from DS children showed a significant increase in insulin resistance marker pIRS1(Ser636) and hyperactivation of the Akt/mTOR/p70S6K pathway downstream from IRS1, possibly driven by higher inhibition of PTEN. Additionally, high levels of pGSK3 beta(Ser9) were also observed. These alterations in the insulin-signaling/mTOR pathways are believed to be early events in the DS brain, contributing to the cognitive dysfunction and intellectual disability seen in this unique population.
ALZHEIMERS & DEMENTIA
(2022)
Article
Integrative & Complementary Medicine
Zhang Wei, Bai Shan-Shan, Zhang Qi, Shi Ru-Ling, Wang He-Cheng, Liu You-Cai, Ni Tian-Jun, Wu Ying, Yao Zhao-Yang, Sun Yi, Wang Ming-Yong
Summary: Physalin B can effectively reduce BACE1 expression to decrease Aβ secretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.
CHINESE JOURNAL OF NATURAL MEDICINES
(2021)
Review
Neurosciences
Karolina Kaminska, Michal Ciolek, Krzysztof Krysta, Marek Krzystanek
Summary: This study evaluated the effectiveness of lower extremity exercise interventions, especially treadmill training, in children and adults with Down syndrome. The results showed that combining treadmill training with physiotherapy can improve the mental and physical health of individuals with Down syndrome across different age groups.
Article
Education, Special
D. Valentini, C. Di Camillo, N. Mirante, G. Vallogini, N. Olivini, A. Baban, L. Buzzonetti, A. Galeotti, M. Raponi, A. Villani
Summary: This study investigated the congenital malformations and main comorbidities of a cohort of children and young people with Down syndrome (DS) in Italy. The findings showed that DS patients have different medical conditions compared to the typical pediatric population, with younger children being more prone to upper respiratory tract infections and being underweight, while older individuals have higher rates of dental diseases, refractive errors, obesity, and autoimmune hypothyroidism.
JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
(2021)
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)
Review
Biochemistry & Molecular Biology
Brian J. Lopresti, Sarah K. Royse, Chester A. Mathis, Savannah A. Tollefson, Rajesh Narendran
Summary: With the emergence of PET, psychiatry gained access to a non-invasive tool for assessing human brain function. Early applications focused on measuring blood flow and metabolism, but specific probes for dopamine and serotonin receptors were later developed. However, the development of monoamine-enhancing drugs was not very successful, leading to a shift in drug development towards other targets. In recent years, PET imaging techniques have also been developed for studying non-monoamine targets.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Sarah K. Royse, Brian J. Lopresti, Chester A. Mathis, Savannah Tollefson, Rajesh Narendran
Summary: Early PET applications in psychiatry aimed to identify cerebral blood flow and metabolism abnormalities, but the need for more specific neurochemical imaging probes became evident. The development of monoaminergic PET radiopharmaceuticals was driven by the belief in the centrality of monoamine dysfunction in psychiatric disorders. However, as drug development shifted away from monoamines, new PET imaging agents for non-monoamine targets were developed. Part two of the review focuses on clinical research studies using these novel targets and radiotracers across different psychiatric disorders.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Geriatrics & Gerontology
Minjie Wu, Noah Schweitzer, Bistra E. Iordanova, Edythe Halligan-Eddy, Dana L. Tudorascu, Chester A. Mathis, Brian J. Lopresti, M. Ilyas Kamboh, Ann D. Cohen, Beth E. Snitz, William E. Klunk, Howard J. Aizenstein
Summary: This study explored the interactive effects of small vessel disease (SVD) and amyloid-beta (Aβ) pathology on hippocampal functional connectivity and volume in cognitively normal older adults. The results showed that in older adults with white matter hyperintensities (WMH+), higher Aβ burden was associated with increased hippocampal local connectivity and lower gray matter density in the medial temporal lobe (MTL). In older adults without WMH, higher Aβ burden was associated with increased hippocampal distal connectivity and no changes in MTL gray matter density. These findings provide support for a hippocampal excitotoxicity model linking SVD to neurodegeneration and the progression to Alzheimer's disease (AD).
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Douglas T. Leffa, Joao Pedro Ferrari-Souza, Bruna Bellaver, Cecile Tissot, Pamela C. L. Ferreira, Wagner S. Brum, Arthur Caye, Jodie Lord, Petroula Proitsi, Thais Martins-Silva, Luciana Tovo-Rodrigues, Dana L. Tudorascu, Victor L. Villemagne, Ann D. Cohen, Oscar L. Lopez, William E. Klunk, Thomas K. Karikari, Pedro Rosa-Neto, Eduardo R. Zimmer, Brooke S. G. Molina, Luis Augusto Rohde, Tharick A. Pascoal
Summary: The genetic liability for attention-deficit/hyperactivity disorder (ADHD) is associated with cognitive decline and the development of Alzheimer's Disease (AD) pathology, especially in individuals with increased amyloid-beta (Aβ) deposition.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Antoine Drieu, Siling Du, Steffen E. Storck, Justin Rustenhoven, Zachary Papadopoulos, Taitea Dykstra, Fenghe Zhong, Kyungdeok Kim, Susan Blackburn, Tornike Mamuladze, Oscar Harari, Celeste M. Karch, Randall J. Bateman, Richard Perrin, Martin Farlow, Jasmeer Chhatwal, Song Hu, Gwendalyn J. Randolph, Igor Smirnov, Jonathan Kipnis
Summary: The study reveals that parenchymal border macrophages (PBMs) are new cellular regulators of cerebrospinal fluid (CSF) flow dynamics. PBMs drive CSF flow by regulating arterial motion and ensuring the smooth access of CSF to perivascular spaces. Decreased PBMs lead to accumulation of extracellular matrix proteins, blocking CSF flow and impairing perfusion and clearance in the central nervous system (CNS). Aging and Alzheimer's disease (AD) affect the function of PBMs, which can be restored by intracisternal injection of macrophage colony-stimulating factor.
Article
Radiology, Nuclear Medicine & Medical Imaging
Bieneke Janssen, Guilong Tian, Zsofia Lengyel-Zhand, Chia-Ju Hsieh, Marshall G. Lougee, Aladdin Riad, Kuiying Xu, Catherine Hou, Chi-Chang Weng, Brian J. Lopresti, Hee Jong Kim, Vinayak V. Pagar, John J. Ferrie, Benjamin A. Garcia, Chester A. Mathis, Kelvin Luk, E. James Petersson, Robert H. Mach
Summary: In this study, a new radioligand with high affinity (<10 nM) for α-synuclein fibrils and PD tissue was identified through a similarity search. This study suggests that a simple in silico approach is a promising strategy to identify novel ligands for target proteins in the CNS and can be radiolabeled for PET neuroimaging studies.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Clinical Neurology
Sigan L. Hartley, Benjamin Handen, Dana Tudorascu, Laisze Lee, Annie Cohen, Emily K. Schworer, Jamie C. Peven, Matthew Zammit, William Klunk, Charles Laymon, Davneet Minhas, Weiquan Luo, Shahid Zaman, Beau Ances, Gregory Preboske, Bradley T. Christian
Summary: This study investigates the AT(N) biomarker characteristics in Down syndrome (DS). The findings suggest that Tau PET (T+) is closely associated with memory impairment and AD clinical status in DS.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Matthew D. Zammit, Tobey J. Betthauser, Andrew K. Mcvea, Charles M. Laymon, Dana L. Tudorascu, Sterling C. Johnson, Sigan L. Hartley, Alexander K. Converse, Davneet S. Minhas, Shahid H. Zaman, Beau M. Ances, Charles K. Stone, Chester A. Mathis, Annie D. Cohen, William E. Klunk, Benjamin L. Handen, Bradley T. Christian
Summary: Understanding the trajectories of AD biomarkers in individuals with Down syndrome (DS) is crucial for clinical interventions and interpretation of drug-related changes.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Sigan L. Hartley, Victoria Fleming, Emily K. Schworer, Jamie Peven, Benjamin L. Handen, Sharon Krinsky-McHale, Christy Hom, Laisze Lee, Dana L. Tudorascu, Charles Laymon, Davneet Minhas, Weiquan Luo, Annie Cohen, Shahid Zaman, Beau M. Ances, Mark Mapstone, Elizabeth Head, Florence Lai, H. Diana Rosas, William Klunk, Bradley Christian
Summary: This study aimed to investigate whether premorbid intellectual disability level was associated with the variability in age-trajectories of Alzheimer's disease biomarkers and cognitive impairments. The results showed no significant effect of premorbid intellectual disability level on the trajectories of Alzheimer's disease biomarkers and cognitive outcomes.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Psychiatry
Akiko Mizuno, Helmet Talib Karim, Maria J. Ly, Brian J. Lopresti, Ann D. Cohen, Areej A. Ali, Chester A. Mathis, William E. Klunk, Howard J. Aizenstein, Beth E. Snitz
Summary: The study aimed to explore the symptoms of subjective cognitive decline (SCD) using fMRI brain activity and investigate the association with amyloid-beta (Ass) load. The results showed that SCD severity was associated with lower dorsomedial thalamus activation.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Cell Biology
Joao Pedro Ferrari-Souza, Bruna Bellaver, Pamela C. L. Ferreira, Andrea L. Benedet, Guilherme Povala, Firoza Z. Lussier, Douglas T. Leffa, Joseph Therriault, Cecile Tissot, Carolina Soares, Yi-Ting Wang, Mira Chamoun, Stijn Servaes, Arthur C. Macedo, Marie Vermeiren, Gleb Bezgin, Min Su Kang, Jenna Stevenson, Nesrine Rahmouni, Vanessa Pallen, Nina Margherita Poltronetti, Ann Cohen, Oscar L. Lopez, William E. Klunk, Jean-Paul Soucy, Serge Gauthier, Diogo O. Souza, Gallen Triana-Baltzer, Ziad S. Saad, Hartmuth C. Kolb, Thomas K. Karikari, Victor L. Villemagne, Dana L. Tudorascu, Nicholas J. Ashton, Henrik Zetterberg, Kaj Blennow, Eduardo R. Zimmer, Pedro Rosa-Neto, Tharick A. Pascoal
Summary: The APOE ε4 allele enhances the long-term effects of Aβ protein on the phosphorylated accumulation of tau protein, which may be mediated by the increased longitudinal plasma phosphorylated tau protein at threonine 217. This long-term accumulation of tau protein is accompanied by brain atrophy and clinical progression.
Article
Clinical Neurology
Nazek Queder, Michael J. Phelan, Lisa Taylor, Nicholas Tustison, Eric Doran, Christy Hom, Dana Nguyen, Florence Lai, Margaret Pulsifer, Julie Price, William C. Kreisl, Herminia D. Rosas, Sharon Krinsky-McHale, Adam M. Brickman, Michael A. Yassa, Nicole Schupf, Wayne Silverman, Ira T. Lott, Elizabeth Head, Mark Mapstone, David B. Keator
Summary: Research suggests a link between Alzheimer's Disease in Down Syndrome (DS) and the overproduction of amyloid plaques. PET technology can be used to assess the amyloid load in specific brain regions. Creating disorder-specific atlases for DS provides more accurate quantification of PET signals compared to using atlases derived from neurotypical populations.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2022)