Article
Clinical Neurology
Caterina Motta, Martina Assogna, Chiara Giuseppina Bonomi, Alfredo Paolo Mascolo, Vincenzo De Lucia, Roberta Semprini, Nicola Biagio Mercuri, Giacomo Koch, Alessandro Martorana
Summary: The study reveals a significant dependency of CSF t-tau levels on diabetes mellitus for APOE E4+ AD patients; Using A beta(1-42) and p-tau biomarkers is effective in discriminating between pathological changes in AD patients; Glucose metabolism dysfunction interacts with tau protein and APOE genotype to affect the pathological process.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Minjeong Jang, Nakwon Choi, Hong Nam Kim
Summary: This study investigates the changes in brain microvasculature and neurons under hyperglycemic conditions using a neurovasculature-on-a-chip model. The results suggest that SIRT1 may be a key regulator of hyperglycemia-induced AD, and that interventions to restore glucose levels can rescue the progression of the disease.
Review
Pharmacology & Pharmacy
Maricarmen Hernandez-Rodriguez, Cecilia Flores Clemente, Martha Edith Macias-Perez, Rolando Alberto Rodriguez-Fonseca, M. Ines Nicolas Vazquez, Joel Martinez, Rene Miranda Ruvalcaba, Martin Martinez Rosas, Elvia Mera Jimenez
Summary: This review focuses on the association between diabetes and Alzheimer's disease (AD), highlighting the mechanisms by which hyperglycemia-induced overactivation of microglia leads to neuroinflammation and neuronal damage, contributing to the pathology of AD.
PHARMACOLOGICAL REPORTS
(2022)
Article
Cell Biology
Shweta Kishor Sonawane, Vladimir N. Uversky, Subashchandrabose Chinnathambi
Summary: The study demonstrated the potential neuroprotective effect of Baicalein in inhibiting aggregation of human Tau protein, dissolving pre-formed fibrils, and being non-toxic to neuronal cells. Baicalein could be considered a lead molecule in combating Tau pathology in Alzheimer's disease.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Biochemistry & Molecular Biology
Filippa Lo Cascio, Paola Marzullo, Rakez Kayed, Antonio Palumbo Piccionello
Summary: This review highlights recent research on modifying the structure of curcumin to search for new effective therapeutic agents against neurodegenerative diseases, with a particular focus on Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Vasileios Papaliagkas, Kallirhoe Kalinderi, Patroklos Vareltzis, Despoina Moraitou, Theodora Papamitsou, Maria Chatzidimitriou
Summary: Alzheimer's disease (AD) is a rapidly growing disease that urgently requires early diagnosis and treatment. Cerebrospinal fluid (CSF), which directly contacts the brain's extracellular space, is the most useful biological fluid for reflecting molecular events in the brain. Proteins and molecules that reflect the pathogenesis of AD, including neurodegeneration, accumulation of Abeta, hyperphosphorylation of tau protein, and apoptosis, can be used as biomarkers. The most commonly used CSF biomarkers for AD are total tau, phospho-tau, and Abeta42.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Batbayar Tumurbaatar, Anna Fracassi, Pietro Scaduto, Jutatip Guptarak, Randall Woltjer, Daniel Jupiter, Giulio Taglialatela
Summary: This study investigates the association of autophagy with cognitive integrity in individuals with Alzheimer's disease neuropathology but without dementia. The results suggest that preserved autophagy may protect against cognitive decline in these individuals.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Longfei Li, Jin Miao, Dandan Chu, Nana Jin, Yunn Chyn Tung, Chun-Ling Dai, Wen Hu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Summary: Findings from this study suggest that the monoclonal tau antibody 77G7 effectively suppresses the seeding activity of AD O-tau and could potentially be developed as an immunotherapeutic drug to inhibit the propagation of tau pathology in AD and related tauopathies.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Clinical Neurology
Shuai Zhao, Ziqi Fan, Xinyi Zhang, Zheyu Li, Ting Shen, Kaicheng Li, Yaping Yan, Yunfeng Yuan, Jiali Pu, Jun Tian, Zhirong Liu, Yanxing Chen, Baorong Zhang
Summary: This study found that metformin can inhibit the propagation of tau protein in Alzheimer's disease and reduce its hyperphosphorylation. It also improves learning and memory deficits, suggesting that metformin could be a promising drug for the prevention and early treatment of AD.
Article
Biochemistry & Molecular Biology
Lei Liu, Yuqi Cai, Bianca M. Lauro, Angela L. Meunier, Jasmeer Chhatwal, Dennis J. Selkoe
Summary: This study aimed to establish a method for generating accurate calibrators as biomarkers for Alzheimer's disease. A semi-synthetic p-Tau181 calibrator was produced by coupling a recombinant tau fragment with a synthetic peptide containing a phosphorylated residue. The calibrator showed a low limit of quantification of 0.14 pg/ml when tested on multiple platforms. This simple and cost-effective method can be used to generate tau pT181 calibrators suitable for different immunoassay platforms and can be easily adapted for other phosphorylated epitopes relevant to Alzheimer's disease.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Neurosciences
Riya Chakrabarty, Sumaira Yousuf, Mahendra P. Singh
Summary: Alzheimer's disease is a cause of dementia that involves protein accumulation and abnormal modification. There is a potential link between AD and diabetes, and SUMOylation plays a crucial role in the pathogenesis of AD. Drosophila melanogaster is an effective model organism for studying the effects of blood glucose levels on AD.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Medicine, General & Internal
Billie J. Matchett, Sarah J. Lincoln, Matt Baker, Nikoleta Tamvaka, Sydney A. Labuzan, Tiffany Hicks N. Sirmans, Christina M. Moloney, Jacqueline Helminger, Kelly M. Hinkle, Janisse Cabrera-Rodriguez, Daniel P. Wickland, Patrick W. Johnson, Michael G. Heckman, Joseph S. Reddy, Steven G. Younkin, Minerva M. Carrasquillo, Ranjan Duara, Neill R. Graff-Radford, Cyril Pottier, Niluefer Ertekin-Taner, Owen A. Ross, Rosa Rademakers, Dennis W. Dickson, Melissa E. Murray
Summary: We investigated the involvement of genetic variants in the SERPINA5 gene in Alzheimer's disease (AD) and found a rare missense variant (p.E228Q) that was present in a small percentage of AD cases. However, there was no significant difference in demographic or clinicopathologic characteristics between carriers and noncarriers of this variant. Moreover, our findings suggest that SERPINA5 genetic variants may not play a major role in clinicopathologic differences in AD.
Article
Clinical Neurology
Madeline S. Morrison, Hugo J. Aparicio, Kaj Blennow, Henrik Zetterberg, Nicholas J. Ashton, Thomas K. Karikari, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Michael A. Sugarman, Brandon Frank, Eric G. Steinberg, Katherine W. Turk, Andrew E. Budson, Rhoda Au, Lee E. Goldstein, Gyungah R. Jun, Neil W. Kowall, Ronald Killiany, Wei Qiao Qiu, Robert A. Stern, Jesse Mez, Ann C. McKee, Thor D. Stein, Michael L. Alosco
Summary: In one of the largest studies of its kind, researchers found that ante-mortem plasma phosphorylated-tau(181) concentrations can accurately differentiate brain donors with and without Alzheimer's disease. This blood test could serve as a minimally invasive and cost-effective tool for the detection and monitoring of Alzheimer's disease.
Article
Clinical Neurology
Emma M. Coomans, Jori Tomassen, Rik Ossenkoppele, Sandeep S. Golla, Marijke den Hollander, Lyduine E. Collij, Emma Weltings, Sophie M. van der Landen, Emma E. Wolters, Albert D. Windhorst, Frederik Barkhof, Eco J. C. de Geus, Philip Scheltens, Pieter Jelle Visser, Bart N. M. van Berckel, Anouk den Braber
Summary: Coomans et al. found substantial similarities in tau load and spatial distribution among identical twins, indicating a significant role of genetic factors in tau pathology. However, differences between twin pairs suggest the influence of environmental factors in tau accumulation. This study provides insights into factors associated with tau pathology and may be important for preventive strategies against Alzheimer's disease.
Article
Clinical Neurology
Alfonso Martinisi, Martin Flach, Frederik Sprenger, Stephan Frank, Markus Tolnay, David T. Winkler
Summary: The study showed that toxic tau species causing neuronal dysfunction can be cleared without inducing seeding effects, suggesting an effective therapeutic intervention in tauopathies. Moreover, recovered mice did not develop more motor impairment or tau pathology in the long term compared to control groups.
Article
Clinical Neurology
Stephen A. Goutman, Kai Guo, Masha G. Savelieff, Adam Patterson, Stacey A. Sakowski, Hani Habra, Alla Karnovsky, Junguk Hur, Eva L. Feldman
Summary: By performing untargeted metabolomics in two independent ALS cohorts, this study identifies recurring pathways that are altered in both cohorts. Many of the pathways are involved in lipid metabolism, including beta-oxidation intermediates and complex and signalling lipids, such as sphingolipids and diacylglycerols.
Article
Endocrinology & Metabolism
Kai Guo, Masha G. Savelieff, Amy E. Rumora, Fadhl M. Alakwaa, Brian C. Callaghan, Junguk Hur, Eva L. Feldman
Summary: This study aimed to identify the plasma metabolomics and lipidomics signature that underlies PN in individuals with average class 3 obesity. The analysis showed significant differences in metabolites and lipids between lean and obese individuals, regardless of PN status. Stratification by PN status within obese individuals revealed differences in specific metabolic and lipid pathways.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Public, Environmental & Occupational Health
Stephen A. Goutman, Jonathan Boss, Christopher Godwin, Bhramar Mukherjee, Eva L. Feldman, Stuart A. Batterman
Summary: Occupational exposure to particulate matter, volatile organic compounds, metals, pesticides, and combustion and diesel exhaust, as well as employment in production occupations, are associated with an increased risk of ALS.
INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
(2022)
Article
Biochemistry & Molecular Biology
Junguk Hur, Ximena Paez-Colasante, Claudia Figueroa-Romero, Ting-wen Lo, Sami J. Barmada, Michelle T. Paulsen, Mats Ljungman, Fadhl M. Alakwaa, Masha G. Savelieff, Stephen A. Goutman, Eva L. Feldman
Summary: This study analyzes the miRNA profiles in patients with amyotrophic lateral sclerosis (ALS) and identifies different miRNA levels in different ALS mutation types. The study also reveals pathways related to ALS and suggests potential targets for future research. These findings contribute to the early diagnosis of ALS.
HUMAN MOLECULAR GENETICS
(2022)
Article
Clinical Neurology
Stephen A. Goutman, Jonathan Boss, Gayatri Iyer, Hani Habra, Masha G. Savelieff, Alla Karnovsky, Bhramar Mukherjee, Eva L. Feldman
Summary: This study found that ALS participants experienced weight loss in the 5 years before enrollment, and long-term decrease in BMI was associated with lower survival rates. Metabolomic profiles were also found to be associated with BMI trajectories. Replicating these findings in other cohorts is necessary.
Review
Endocrinology & Metabolism
Melissa A. Elafros, Brian C. Callaghan, Lesli E. Skolarus, Loretta Vileikyte, John G. Lawrenson, Eva L. Feldman
Summary: Knowledge about microvascular complications of diabetes varies among patients and healthcare providers, with factors such as education level, disease duration, and socioeconomic status influencing patient knowledge. Misconceptions regarding appropriate screening practices for complications are common among healthcare providers. Further research is needed to identify interventions that can improve knowledge and outcomes for both patients and providers.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Article
Clinical Neurology
Stephen A. Goutman, Jonathan Boss, Christopher Godwin, Bhramar Mukherjee, Eva L. Feldman, Stuart A. Batterman
Summary: This study aimed to investigate the associations between occupational settings, self-reported occupational exposures, and survival and onset segment of ALS. The findings suggest that work in production occupations, military occupations, and self-reported occupational pesticide exposure are associated with poorer survival. Furthermore, specific occupational settings and exposures are associated with different onset segments of ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Stephanie A. Eid, Mohamed Noureldein, Bhumsoo Kim, Lucy M. Hinder, Faye E. Mendelson, John M. Hayes, Junguk Hur, Eva L. Feldman
Summary: This study characterized the transcriptional profiles and intercellular communication of Schwann cells (SCs) in a mouse model of prediabetes and neuropathy. The results revealed that SCs can adapt to metabolic stress and inflammation by altering their intercellular communication, which influences the progression of nerve pathophysiology. This study provides important insights into the function and communication mechanisms of SCs in nerve pathology.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Neurosciences
Stephanie A. Eid, Amy E. Rumora, Bogdan Beirowski, David L. Bennett, Junguk Hur, Masha G. Savelieff, Eva L. Feldman
Summary: The prevalence of diabetes is increasing due to the aging population, with type 2 diabetes being the most common type. Diabetic peripheral neuropathy is a complication that damages peripheral nerves and is influenced by metabolic and bioenergetic dysfunction. Recent evidence suggests that obesity and dyslipidemia also contribute to this condition.
Article
Clinical Neurology
Ayse J. Muniz, Tugba Topal, Michael D. Brooks, Angela Sze, Do Hoon Kim, Jacob Jordahl, Joe Nguyen, Paul H. Krebsbach, Masha G. Savelieff, Eva L. Feldman, Joerg Lahann
Summary: In this study, scientists developed an engineered extracellular matrix (EECM) to provide support and cell-to-matrix interactions for developing brain organoids. Compared to conventional protein matrix, EECMs enhanced neurogenesis, glial maturation, and neuronal diversity. The EECMs also supported long-term culture and produced brain organoids with increased protein diversity.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Rosemary E. Henn, Kai Guo, Sarah E. Elzinga, Mohamed H. Noureldein, Faye E. Mendelson, John M. Hayes, Diana M. Rigan, Masha G. Savelieff, Junguk Hur, Eva L. Feldman
Summary: Obesity is a global concern associated with cognitive impairment. It induces brain inflammation and activates microglia, leading to synaptic spine phagocytosis and cognitive impairment. The mechanisms of microglial activation during obesity are not fully understood.
Article
Clinical Neurology
Stephen A. Goutman, Jonathan Boss, Dae-Gyu Jang, Bhramar Mukherjee, Rudy J. Richardson, Stuart Batterman, Eva L. Feldman
Summary: This study aimed to replicate previous findings regarding the association between persistent organic pollutants (POPs) and amyotrophic lateral sclerosis (ALS) risk and survival. The analysis of samples from 164 ALS patients and 105 control participants showed that several POPs were significantly associated with ALS risk, and the combined mixture of all POPs was associated with ALS survival.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Clinical Neurology
Stephen A. Goutman, Masha G. Savelieff, Dae-Gyu Jang, Junguk Hur, Eva L. Feldman
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration, with both genetic and environmental factors contributing to the risk and rate of disease progression. Epidemiological studies suggest potential contributions to the ALS exposome from pesticides, occupational exposures, sports and physical activity, metals, air pollution, trauma, electromagnetic fields, the gut microbiome, diet and lifestyle factors. The mechanisms underlying the effects of environmental factors on ALS risk remain incompletely understood but might involve neurotoxicity from specific environmental toxins, microbiome-mediated changes, epigenetic restructuring, systemic and central inflammation, and excitotoxicity. Most studies of the ALS exposome have a retrospective design using questionnaires and are, therefore, prone to recall bias and other limitations. Future studies will require prospective, longitudinal designs that include quantification of exposures in biosamples in addition to questionnaires.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
In-Young Choi, Wen-Tung Wang, Bhumsoo Kim, Junguk Hur, David C. Robbins, Dae-Gyu Jang, Masha G. Savelieff, Eva L. Feldman, Phil Lee
Summary: This study characterized the metabolic changes in the brain of patients with T2D using in vivo H-1 magnetic resonance spectroscopy. Elevated levels of several metabolites were observed in both T2D patients and T2D mice, indicating the impact of poorly controlled hyperglycemia on brain metabolism. The study demonstrates the utility of H-1 magnetic resonance spectroscopy in monitoring and understanding the metabolic changes in T2D progression.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Clinical Neurology
Melissa A. Elafros, Henning Andersen, David L. Bennett, Masha G. Savelieff, Vijay Viswanathan, Brian C. Callaghan, Eva L. Feldman
Summary: Diabetic peripheral neuropathy is a common complication of diabetes, and early diagnosis and treatment are crucial for improving patients' quality of life. Hyperglycemia and metabolic syndrome are major risk factors for the development of diabetic peripheral neuropathy.