Article
Clinical Neurology
Valeria Isella, Daniele Licciardo, Giulia Nastasi, Valentina Impagnatiello, Francesca Ferri, Cristina Mapelli, Cinzia Crivellaro, Monica Musarra, Sabrina Morzenti, Ildebrando Appollonio, Carlo Ferrarese
Summary: Late-onset and early-onset dementia exhibit neurobiological and clinical differences. This study compared the clinical and FDG-PET features of posterior cortical atrophy (PCA), the visual variant of Alzheimer's disease, between late-onset and early-onset cases. The results showed that the main difference between the two groups was a higher prevalence of Balint-Holmes symptoms in the early-onset cases, which was associated with severe bilateral occipito-temporo-parietal hypometabolism. In the late-onset cases, there was a reduction of FDG uptake mainly in the right posterior regions. Age was found to be correlated with metabolism in different brain regions.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
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
Dror Shir, Jonathan Graff-Radford, Mary M. Machulda, Nha Trang Thu Pham, Clifford R. Jack, Val J. Lowe, Jennifer L. Whitwell, Keith A. Josephs
Summary: This study found that primary occipital posterior cortical atrophy (PCA) is characterized by an older age at onset, more color perception dysfunction, less severe ideomotor apraxia, and less hypometabolism in the temporo-parietal meta-ROI compared to established phenotypes.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Anna Bartoletti-Stella, Martina Tarozzi, Giacomo Mengozzi, Francesca Asirelli, Laura Brancaleoni, Nicola Mometto, Michelangelo Stanzani-Maserati, Simone Baiardi, Simona Linarello, Marco Spallazzi, Roberta Pantieri, Elisa Ferriani, Paolo Caffarra, Rocco Liguori, Piero Parchi, Sabina Capellari
Summary: This study reveals the genetic contribution to early-onset Alzheimer's disease (EOAD) in Italian patients. Specific gene variants have been identified as risk factors for EOAD, and the combination of these variants can explain a significant proportion of cases. Comprehensive genetic screening is important for clinical purposes and understanding the overlapping pathogenic mechanisms between different forms of dementia.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Medicine, General & Internal
Tanzil Rujeedawa, Eva Carrillo Felez, Isabel C. H. Clare, Juan Fortea, Andre Strydom, Anne-Sophie Rebillat, Antonia Coppus, Johannes Levin, Shahid H. Zaman
Summary: Genetic and acquired Alzheimer's disease have different clinical and pathological characteristics, with Down syndrome-associated AD and Autosomal Dominant AD appearing in younger populations with a wider range of manifestations, while late-onset AD is mainly influenced by age-related comorbidities.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Clinical Neurology
Xu-Ying Li, Yue Cui, Donglai Jing, Kexin Xie, Xiaoling Zhong, Yu Kong, Yuting Wang, Min Cha, Chaodong Wang, Liyong Wu
Summary: This study identified rare damaging variants associated with sEOAD and PCA through whole-exome sequencing, expanding the genetic and phenotypic spectrums of these diseases.
ALZHEIMER DISEASE & ASSOCIATED DISORDERS
(2021)
Article
Endocrinology & Metabolism
Sudharsana Sundarrajan, Arthi Venkatesan, S. Udhaya Kumar, Mohanraj Gopikrishnan, Iftikhar Aslam Tayubi, M. Aditya, Gowrishankar Bychapur Siddaiah, C. George Priya Doss, Hatem Zayed
Summary: Alzheimer's disease is a leading cause of dementia in elderly patients, with a duration of 3 to 11 years after diagnosis. The incidence of AD is increasing significantly in East Asian countries. The disease involves memory loss, behavioral issues, and cognitive impairment. The study investigates the whole exome sequences of LOAD patients of Korean origin to identify rare genetic variants that may contribute to the disorder.
METABOLIC BRAIN DISEASE
(2023)
Article
Clinical Neurology
Mario Torso, Samrah Ahmed, Christopher Butler, Giovanna Zamboni, Mark Jenkinson, Steven Chance
Summary: Global cortical DTI derived measures were able to detect differences in both PCA and tAD patients compared to healthy controls. AngleR was the best measure to discriminate HC from tAD (AUC = 0.922), while PerpPD was the best measure to discriminate HC from PCA (AUC = 0.961). Finally, the best global measure to differentiate the two patient groups was ParlPD (AUC = 0.771).
JOURNAL OF NEUROLOGY
(2021)
Article
Neurosciences
Oleg Yerstein, Leila Parand, Li-Jung Liang, Adrienne Isaac, Mario F. Mendez
Summary: The study reviewed the clinical experience of 65 patients with PCA from 1995 to 2020, finding that most patients presented with visual localization complaints and visuospatial symptoms, with memory complaints and depression also common. Neurobehavioral testing showed difficulties in visuospatial constructions, memory, and naming in these patients. The research suggests modifying PCA criteria to include secondary memory and naming difficulties, as well as emphasizing the presence of Gerstmann's and Balint's syndromes.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neuroimaging
Neha Atulkumar Singh, Arvin Arani, Jonathan Graff-Radford, Matthew L. Senjem, Peter R. Martin, Mary M. Machulda, Christopher G. Schwarz, Yunhong Shu, Petrice M. Cogswell, David S. Knopman, Ronald C. Petersen, Val J. Lowe, Clifford R. Jack Jr, Keith A. Josephs, Jennifer L. Whitwell
Summary: This study used QSM to detect iron distribution in the brain and found differences in iron deposition patterns between typical AD and atypical AD (such as LPA and PCA). The results demonstrate the potential of QSM in studying iron deposition in these patients.
NEUROIMAGE-CLINICAL
(2022)
Article
Clinical Neurology
Marie-Anne St-Georges, Linshan Wang, Marianne Chapleau, Raffaella Migliaccio, Thomas Carrier, Maxime Montembeault
Summary: This study compared the behavioral symptoms of individuals with early-stage posterior cortical atrophy (PCA) to healthy controls and other Alzheimer's disease variants. The results showed that PCA patients often experience anxiety, depression, apathy, and irritability. They also exhibited disorganized and reactive behaviors during cognitive testing. However, their social cognition and empathy were generally preserved. This study provides valuable insights into the non-visual symptoms of PCA and has implications for diagnosis and intervention strategies.
JOURNAL OF NEUROLOGY
(2023)
Review
Cell Biology
Thibaut Gauvrit, Hamza Benderradji, Luc Buee, David Blum, Didier Vieau
Summary: As the population ages, the incidence of neurodegenerative disorders, particularly Alzheimer's disease, has increased dramatically. AD is a complex disease affected by both genetic and environmental factors, with epigenetic mechanisms playing a role. Early environmental exposure and epigenetic mechanisms may influence the development of late-onset AD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Mario F. Mendez, Youssef Khattab, Oleg Yerstein
Summary: The study showed that impaired visual search tasks of spatial localization can effectively differentiate patients with PCA from those with tAD and HC, highlighting the importance of visual search tasks in detecting and distinguishing PCA from more common dementia syndromes.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Gregory Kuchcinski, Lucas Patin, Renaud Lopes, Melanie Leroy, Xavier Delbeuck, Adeline Rollin-Sillaire, Thibaud Lebouvier, Yi Wang, Pascal Spincemaille, Thomas Tourdias, Lotfi Hacein-Bey, David Devos, Florence Pasquier, Xavier Leclerc, Jean-Pierre Pruvo, Sebastien Verclytte
Summary: This study aimed to investigate the brain iron distribution patterns in subtypes of early-onset Alzheimer's disease (EOAD) using quantitative susceptibility mapping (QSM). The results showed that EOAD patients had higher QSM values in deep gray nuclei and limbic structures compared to controls. Among EOAD subtypes, HpSp(MRI) had the highest QSM values in deep gray nuclei, while LPMRI had the highest QSM values in limbic structures. Iron overload in deep gray nuclei could help identify patients with atypical presentation of Alzheimer's disease.
EUROPEAN RADIOLOGY
(2023)
Article
Environmental Sciences
Jaelim Cho, Heeseon Jang, Hyunji Park, Young Noh, Jungwoo Sohn, Sang-Baek Koh, Seung-Koo Lee, Sun-Young Kim, Changsoo Kim
Summary: This study investigated the effect of air pollution on Alzheimer's disease-specific brain structural pathologies and whether this effect leads to poorer cognitive function. The findings suggest that air pollution exposures may induce AD-like cortical atrophy and lead to poorer cognitive function in dementia-free adults.
ENVIRONMENT INTERNATIONAL
(2023)
Editorial Material
Neurosciences
Alexis Moscoso, Melissa C. Wren, Tammaryn Lashley, Erik Arstad, Melissa E. Murray, Nick C. Fox, Kerstin Sander, Michael Scholl
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Yi Xiao Jiang, Qin Cao, Michael R. Sawaya, Romany Abskharon, Peng Ge, Michael DeTure, Dennis W. Dickson, Janine Y. Fu, Rachel R. Ogorzalek Loo, Joseph A. Loo, David S. Eisenberg
Summary: This study found that amyloid fibrils in FTLD-TDP patients are formed by TMEM106B protein rather than TDP-43 protein. In addition, abundant non-fibrillar aggregated TDP-43 protein was observed.
Article
Multidisciplinary Sciences
D. Jones, V Lowe, J. Graff-Radford, H. Botha, L. Barnard, D. Wiepert, M. C. Murphy, M. Murray, M. Senjem, J. Gunter, H. Wiste, B. Boeve, D. Knopman, R. Petersen, C. Jack
Summary: This study presents a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques. The authors propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology. They also apply the model to normal aging and other degenerative diseases of mental functions.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Shunsuke Koga, Mariam Ishaque, W. Jeffrey Elias, Binit B. Shah, Aya Murakami, Dennis W. Dickson
Summary: This study reports the first postmortem neuropathologic findings of FUS thalamotomy in a patient with tremor-dominant PD. The results suggest that FUS thalamotomy can improve tremor symptoms and cause thalamic lesions, with implications for understanding PD-related pathology. Further pathological assessments are needed.
NPJ PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Aivi T. Nguyen, Naomi Kouri, Sydney A. Labuzan, Scott A. Przybelski, Timothy G. Lesnick, Sheelakumari Raghavan, Robert Reid, R. Ross Reichard, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Michelle M. Mielke, Dennis W. Dickson, Jonathan Graff-Radford, Melissa E. Murray, Prashanthi Vemuri
Summary: This study evaluated the association between neuroimaging measures of cerebrovascular disease (CVD) and neuropathologic CVD scales, finding that dMRI could serve as a meaningful surrogate for CVD assessment and suggesting the development of better quantitative measures using dMRI.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Christina M. Moloney, Sydney A. Labuzan, Julia E. Crook, Habeeba Siddiqui, Monica Castanedes-Casey, Christian Lachner, Ronald C. Petersen, Ranjan Duara, Neill R. Graff-Radford, Dennis W. Dickson, Michelle M. Mielke, Melissa E. Murray
Summary: This study aims to characterize the recognition of phosphorylated tau sites in early neurofibrillary tangle maturity levels, which may explain why these fluid biomarkers can be observed before symptom onset.
ALZHEIMERS & DEMENTIA
(2023)
Article
Chemistry, Organic
Heather M. Stein, Surendra R. Gundam, Aditya Bansal, Nicholas R. Nelson, Geoffry L. Curran, Timothy R. DeGrado, Mark A. Frye, John D. Port, Val J. Lowe, Melissa E. Murray, Mukesh K. Pandey
Summary: This study synthesized two PET probes and evaluated their permeability through the blood-brain barrier and affinity towards GSK-3 alpha/beta. The results showed that [F-18]F-CNPIFE had higher brain uptake compared to [F-18]F-CNBI, making it a promising PET probe for imaging GSK-3 alpha/beta.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Neurosciences
Jaclyn Lilek, Kaouther Ajroud, Alexander Z. Feldman, Sesha Krishnamachari, Shadi Ghourchian, Tamar Gefen, Callen L. Spencer, Allegra Kawles, Qinwen Mao, Jessica F. Tranovich, Clifford R. Jack, M-Marsel Mesulam, R. Ross Reichard, Hui Zhang, Melissa E. Murray, David Knopman, Dennis W. Dickson, Ronald C. Petersen, Benjamin Smith, Karen H. Ashe, Michelle M. Mielke, Kathryn M. Nelson, Margaret E. Flanagan
Summary: Phosphorylated cytoplasmic tau inclusions are correlated with and precede cognitive deficits in Alzheimer's Disease (AD). The results also indicate that the frontal cortex represents early AD, while entorhinal total tau levels are significantly higher in amnestic mild cognitive impairment compared to AD.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Stephanie R. Oatman, Joseph S. Reddy, Zachary Quicksall, Minerva M. Carrasquillo, Xue Wang, Chia-Chen Liu, Yu Yamazaki, Thuy T. Nguyen, Kimberly Malphrus, Michael Heckman, Kristi Biswas, Kwangsik Nho, Matthew Baker, Yuka A. Martens, Na Zhao, Jun Pyo Kim, Shannon L. Risacher, Rosa Rademakers, Andrew J. Saykin, Michael DeTure, Melissa E. Murray, Takahisa Kanekiyo, Dennis W. Dickson, Guojun Bu, Mariet Allen, Niluefer Ertekin-Taner
Summary: By integrating genetic information and data on neurobiochemical markers, we identified seven novel loci and the APOE locus that are associated with Alzheimer's disease. These loci and genes are also related to other relevant variables, gene expression, brain health, and other neuropsychiatric diseases.
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Nicholas B. B. Martin, Shunsuke Koga, Brian S. S. Appleby, Hiroaki Sekiya, Dennis W. Dickson
Summary: Two cases of patients who were misdiagnosed with multiple system atrophy (MSA) actually had Creutzfeldt-Jakob disease (CJD), as confirmed by neuropathological findings. This suggests that when the disease progresses rapidly or the clinical course is atypical, even if clinical features suggest MSA, the possibility of CJD should also be considered.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Letter
Clinical Neurology
Shunsuke Koga, Aya Murakami, Nicholas B. Martin, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Hiroaki Sekiya, Shunsuke Koga, Aya Murakami, Miki Kawazoe, Minji Kim, Nicholas B. Martin, Ryan J. Uitti, William P. Cheshire, Zbigniew K. Wszolek, Dennis W. Dickson
Summary: The study compared the diagnostic accuracy of the MDS criteria and second consensus criteria for MSA, finding that the MDS criteria had higher specificity for clinically established and probable MSA, while the second consensus criteria had higher sensitivity for probable and possible MSA.
Article
Multidisciplinary Sciences
Junhao Li, Manoj K. Jaiswal, Jo-Fan Chien, Alexey Kozlenkov, Jinyoung Jung, Ping Zhou, Mahammad Gardashli, Luc J. Pregent, Erica Engelberg-Cook, Dennis W. Dickson, Veronique V. Belzil, Eran A. Mukamel, Stella Dracheva
Summary: The repeat expansion in the C9orf72 gene is a common genetic cause of ALS and FTD. The study found pervasive alterations in gene expression and chromatin accessibility in neurons and astrocytes of C9-ALS patients, as well as gene expression changes in glial cells of C9-FTD patients. These findings indicate unique molecular disruptions in different cell types, brain regions, and diseases.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Aimee R. Herdt, Hui Peng, Dennis W. Dickson, Todd E. Golde, Elizabeth A. Eckman, Chris W. Lee
Summary: Krabbe disease is a neurologic disorder characterized by the accumulation of psychosine in the CNS. In a mouse model, treatment with AAV1-GALC, a viral vector expressing GALC, significantly improved body weight gain and survival, as well as normalized psychosine levels in the brain.
Letter
Clinical Neurology
Miki Kawazoe, Shunsuke Koga, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)