Review
Biochemistry & Molecular Biology
Eun Hae Kwon, Sabrina Tennagels, Ralf Gold, Klaus Gerwert, Leon Beyer, Lars Toenges
Summary: This paper emphasizes the importance of reliable objective markers for identifying individuals at risk of Parkinson's disease. Advances in biomarker discovery, particularly in the cerebrospinal fluid (CSF), have provided promising preliminary results. Potential biomarkers include alpha-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes, and markers of neuroinflammation. Metabolomics approaches have also offered insights into novel biological pathways. Genetic forms of PD can help identify subgroups suitable for targeted treatments. Further validation studies are needed to determine the most valuable CSF biomarkers or combinations for clinical and research purposes.
Article
Neurosciences
Anna Lidia Wojdala, Davide Chiasserini, Giovanni Bellomo, Silvia Paciotti, Lorenzo Gaetani, Federico Paolini Paoletti, Lucilla Parnetti
Summary: Phosphatidylethanolamine binding protein 1 (PEBP1) has potential as a biomarker for Alzheimer's disease (AD), but further research is needed to evaluate its diagnostic potential.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Multidisciplinary Sciences
Eleanor Sinclair, Drupad K. Trivedi, Depanjan Sarkar, Caitlin Walton-Doyle, Joy Milne, Tilo Kunath, Anouk M. Rijs, Rob M. A. de Bie, Royston Goodacre, Monty Silverdale, Perdita Barran
Summary: This study used metabolomics profiling to identify changes in lipids in the sebum of PD patients, with alterations related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism, and fatty acid biosynthesis. The findings suggest sebum can be a potential source for identifying biomarkers for PD.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Peggy Barschke, Samir Abu-Rumeileh, M. H. D. Rami Al Shweiki, Lorenzo Barba, Federico Paolini Paoletti, Patrick Oeckl, Petra Steinacker, Steffen Halbgebauer, Lorenzo Gaetani, Jan Lewerenz, Albert Christian Ludolph, Georg Bernhard Landwehrmeyer, Lucilla Parnetti, Markus Otto
Summary: Proenkephalin and prodynorphin-derived peptides may serve as potential pathogenic and disease severity markers in Huntington's disease and Parkinson's disease. The levels of these peptides are significantly decreased in Huntington's disease and are associated with disease severity scores. In Parkinson's disease, the levels of these peptides are within the normal range, but higher levels are found in patients treated with dopamine therapy.
JOURNAL OF NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Jiewen Qiu, Guoyou Peng, Yuting Tang, Shiyin Li, Zengfu Liu, Jiayun Zheng, Yunxin Wang, Hanqun Liu, Lijian Wei, Yilin Su, Yuwan Lin, Wei Dai, Zhiling Zhang, Xiang Chen, Liuyan Ding, Wenyuan Guo, Xiaoqin Zhu, Pingyi Xu, Mingshu Mo
Summary: This study established a rat model of Parkinson's disease (PD) using 6-hydroxydopamine (6-OHDA) and analyzed the lipid profile in cerebrospinal fluid (CSF) using lipidomic approaches. The results showed significant effects of 6-OHDA on behavior, dopaminergic neurons, and lipid composition in CSF. Specific lipid families and species exhibited fluctuations during the progression of Parkinson's disease and were correlated with behavioral and pathological changes in the midbrain.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Immunology
Kaja Nordengen, Bjorn-Eivind Kirsebom, Grit Richter, Lene Palhaugen, Berglind Gisladottir, Nikias Siafarikas, Arne Nakling, Arvid Rongve, Geir Brathen, Goril Rolfseng Grontvedt, Fernando Gonzalez, Knut Waterloo, Kulbhushan Sharma, Thomas Karikari, Eleonora M. Vromen, Betty M. Tijms, Pieter J. Visser, Per Selnes, Milicia G. Kramberger, Bengt Winblad, Kaj Blennow, Tormod Fladby
Summary: Brain innate immune activation is associated with Alzheimer's disease, with varying degrees of activation at different disease stages. In predementia AD, differences in immune activation levels and biomarker profiles may be related to amyloidosis and tau pathology. Changes in certain biomarkers in cerebrospinal fluid may be linked to cognitive preservation or impairment in predementia AD.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Federico Paolini Paoletti, Lorenzo Gaetani, Giovanni Bellomo, Elena Chipi, Nicola Salvadori, Chiara Montanucci, Andrea Mancini, Marta Filidei, Pasquale Nigro, Simone Simoni, Nicola Tambasco, Massimiliano Di Filippo, Lucilla Parnetti
Summary: The pathophysiological processes and development of Parkinson's disease with mild cognitive impairment (PD-MCI) are still debated. This study investigated the CSF neurochemical profile and cognitive changes in PD-MCI, cognitively normal PD, prodromal Alzheimer's disease, and individuals with other neurological diseases. CSF biomarkers related to amyloidosis, tauopathy, neurodegeneration, synaptic damage, and glial activation were measured. The results showed that PD-MCI patients had higher levels of NfL/p-NfH ratio compared to PD-CN. Baseline levels of NfL, p-tau, and sTREM2 were associated with worsening cognitive impairment in PD-MCI after 2 years. Further investigations with larger cohorts and neuropathological verification are needed to understand the heterogeneity of PD-MCI.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Yan Li, Suzanne E. Schindler, James G. Bollinger, Vitaliy Ovod, Kwasi G. Mawuenyega, Michael W. Weiner, Shaw M. Leslie, Colin L. Masters, Christopher J. Fowler, John Q. Trojanowski, Magdalena Korecka, Ralph N. Martins, Shorena Janelidze, Oskar Hansson, Randall J. Bateman
Summary: This study demonstrates that plasma A beta 42/A beta 40 assay is an accurate diagnostic tool for classifying amyloid PET status. The assay performs similarly in both cognitively unimpaired and impaired individuals, and its accuracy improves with APOE epsilon 4 carrier status.
Article
Clinical Neurology
Christina D. Orru, Thong C. Ma, Andrew G. Hughson, Bradley R. Groveman, Ankit Srivastava, Douglas Galasko, Rachel Angers, Patrick Downey, Karen Crawford, Samantha J. Hutten, Un Jung Kang, Byron Caughey
Summary: The study shows that an improved assay for diagnosing Parkinson's disease dramatically reduces the diagnosis time while maintaining high performance standards. Positive signals were found in 97% of Parkinson's disease cases compared to only 13% of healthy controls, with weak correlations between assay parameters and clinical measures observed. The assay's efficiency in diagnosing Parkinson's disease is supported by these findings.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Review
Medicine, General & Internal
D. O. T. Alawode, A. J. Heslegrave, N. J. Ashton, T. K. Karikari, J. Simren, L. Montoliu-Gaya, J. Pannee, A. O'Connor, P. S. J. Weston, J. Lantero-Rodriguez, A. Keshavan, A. Snellman, J. Gobom, R. W. Paterson, J. M. Schott, K. Blennow, N. C. Fox, H. Zetterberg
Summary: Alzheimer's disease is increasingly prevalent worldwide, with a need for earlier and more secure diagnosis techniques. Current biomarker-based guidelines for AD diagnosis heavily rely on neuroimaging and CSF sampling, while blood-based biomarkers show potential for more accessible and cost-effective testing. Plasma neurofilament light chain and phosphorylated tau exhibit promise, but further comparisons are needed for p-tau to differentiate AD from non-AD dementias reliably. Plasma amyloid beta could serve as an early screening tool, but requires precise tests and robust pre-analytical protocols.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Cell Biology
Yael Hirschberg, Natalia Valle-Tamayo, Oriol Dols-Icardo, Sebastiaan Engelborghs, Bart Buelens, Roosmarijn E. Vandenbroucke, Yannick Vermeiren, Kurt Boonen, Inge Mertens
Summary: Dementia is a leading cause of death worldwide, and this study focused on analyzing the proteome of cerebrospinal fluid (CSF) and CSF-derived extracellular vesicles (EVs) from patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia. The analysis identified differentially expressed proteins that can be helpful for differential diagnosis and offer new avenues for research into disease-specific pharmacological therapeutics.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Clinical Neurology
Chengjie Xiong, Jingqin Luo, Suzanne E. Schindler, Anne M. Fagan, Tammie Benzinger, Jason Hassenstab, Joyce E. Balls-Berry, Folasade Agboola, Elizabeth Grant, Krista L. Moulder, John C. Morris
Summary: This study found racial differences in the longitudinal changes of Alzheimer's disease biomarkers, with slower deposition of amyloid and different patterns of change in cerebrospinal fluid amyloid beta (Aβ)42 between Blacks and Whites. Additionally, the increase in cerebrospinal fluid total tau and phosphorylated tau181 was lower in Blacks compared to Whites.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Claire Bridel, Charisse Somers, Anne Sieben, Annemieke Rozemuller, Ellis Niemantsverdriet, Hanne Struyfs, Yannick Vermeiren, Christine Van Broeckhoven, Peter P. De Deyn, Maria Bjerke, Guy Nagels, Charlotte E. Teunissen, Sebastiaan Engelborghs
Summary: This study examines the relationship between neuropathology and CSF biomarkers in Alzheimer's disease patients, finding that the associations are stronger and more significant with longer intervals between lumbar puncture and death. This suggests that CSF biomarkers may not be well suited for monitoring neuropathological changes at later disease stages.
Article
Biochemistry & Molecular Biology
Elena Vacchi, Jacopo Burrello, Alessio Burrello, Sara Bolis, Silvia Monticone, Lucio Barile, Alain Kaelin-Lang, Giorgia Melli
Summary: This study characterized and compared distinctive cerebrospinal fluid (CSF)-derived extracellular vesicles (EVs) in patients with Parkinson's Disease (PD) and atypical parkinsonisms (AP), and built a diagnostic model based on immune profiling of EV surface markers using artificial intelligence. The model, constructed using EV markers co-expressed in plasma and CSF, showed high sensitivity (96.6%) and accuracy (92.6%) in discriminating PD from non-PD patients. The research underscores the importance of EV surface markers in inflammation in PD and highlights the role of EVs as pathways/biomarkers for protein aggregation-related neurodegenerative diseases.
Article
Multidisciplinary Sciences
Le Gjerum, Birgitte Bo Andersen, Marie Bruun, Anja Hviid Simonsen, Otto Molby Henriksen, Ian Law, Steen Gregers Hasselbalch, Kristian Steen Frederiksen
Summary: The study found that cerebrospinal fluid biomarkers have a higher clinical value in supporting the diagnosis of Alzheimer's disease compared to 2-[F-18]FDG-PET, affecting diagnostic confidence and the need for ancillary investigations significantly.
Article
Medicine, Research & Experimental
Zi H. Su, Salil Patel, Bronwyn Gavine, Tim Buchanan, Marko Bogdanovic, Nagaraja Sarangmat, Alexander L. Green, Bastiaan R. Bloem, James J. FitzGerald, Chrystalina A. Antoniades
Summary: This study compared the effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN DBS) on gait variability in Parkinson disease patients. The results showed that STN DBS reduced short-term variability in lower limb gait parameters, while medication did not have this effect. In addition, STN DBS had no effect on arm swing and trunk motion variability, while medication increased them.
Article
Endocrinology & Metabolism
Tessa M. A. Peters, Jona Merx, Pieter C. Kooijman, Marek Noga, Siebolt de Boer, Loes A. van Gemert, Guido Salden, Udo F. H. Engelke, Dirk J. Lefeber, Rianne E. van Outersterp, Giel Berden, Thomas J. Boltje, Rafael Artuch, Leticia Pias-Peleteiro, Angeles Garcia-Cazorla, Ivo Baric, Beat Thoeny, Jos Oomens, Jonathan Martens, Ron A. Wevers, Marcel M. Verbeek, Karlien L. M. Coene, Michel A. A. P. Willemsen
Summary: Using next-generation metabolic screening, we identified new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS).
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Geriatrics & Gerontology
Lily Man Lee Chan, Oliver Yongyang Yan, Jay Jung Jae Lee, Wendy Wing Tak Lam, Chia-Chin Lin, Man Auyeung, Bastiaan R. Bloem, Jojo Yan Yan Kwok
Summary: Palliative care is associated with lower symptom burden and higher caregiver and patient satisfaction in patients with progressive neurologic diseases. However, the associations are not significant after excluding studies with high risk of bias. The effects of palliative care on caregiver burden and patient quality of life are inconclusive.
JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
(2023)
Article
Clinical Neurology
Amir H. Talebi, Jan H. L. Ypinga, Nienke M. De Vries, Jorik Nonnekes, Marten Munneke, Bas R. Bloem, Tom Heskes, Yoav Ben-Shlomo, Sirwan K. L. Darweesh
Summary: Specialized physiotherapy and occupational therapy can reduce the incidence rate of Parkinson's disease-related complications. There may be a synergistic effect among multiple specialized allied health disciplines. The findings of this study support the introduction of specialized allied health therapy expertise in Parkinson's disease care.
MOVEMENT DISORDERS
(2023)
Editorial Material
Neurosciences
Bastiaan R. Bloem, Lorraine V. Kalia
JOURNAL OF PARKINSONS DISEASE
(2023)
Letter
Clinical Neurology
Anna M. de Kort, H. Bea Kuiperij, Floris H. B. M. Schreuder, Catharina J. M. Klijn, Marcel M. Verbeek
ANNALS OF NEUROLOGY
(2023)
Article
Neurosciences
Emma van den Berg, Johanna Nilsson, Iris Kersten, Gunnar Brinkmalm, Anna M. de Kort, Catharina J. M. Klijn, Floris H. B. M. Schreuder, Lieke Jakel, Johan Gobom, Erik Portelius, Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow, H. Bea Kuiperij, Marcel M. Verbeek
Summary: This study investigated synaptic dysfunction in cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). The results showed that synaptic protein levels were largely unchanged in CAA patients, while they were significantly increased in AD patients. It was also found that abnormal synaptic protein levels were associated with concomitant AD pathology in CAA patients. These findings suggest a differential involvement of synaptic dysfunction in CAA and AD, possibly reflecting distinct pathological mechanisms.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Public, Environmental & Occupational Health
Irene Gottgens, Linda Modderkolk, Corine Jansen, Sirwan K. L. Darweesh, Bastiaan R. Bloem, Sabine Oertelt-Prigione
Summary: This study explores the salience of gender-related aspects in the illness experiences and care provision preferences of people with Parkinson's disease (PD). Most participants did not consider gender-related aspects salient towards their illness experiences, but some described stereotypical views related to visibility of PD, emotional experiences, help seeking, role patterns, and physical appearance. While most participants did not express specific gender-related preferences for their healthcare providers, those that did preferred women as healthcare providers, citing attributed feminine traits relevant in physical examinations of people with PD.
SOCIAL SCIENCE & MEDICINE
(2023)
Review
Neurosciences
Anouk Tosserams, Bastiaan R. Bloem, Kaylena Ehgoetz A. Martens, Rick C. Helmich, Roy P. C. Kessels, James M. Shine, Natasha L. Taylor, Gabriel Wainstein, Simon J. G. Lewis, Jorik Nonnekes
Summary: In stressful situations, individuals with Parkinson's disease (PD) may experience worsening of motor symptoms, including gait impairments. However, some patients report benefits from stressful or high-arousal situations. A study with 4324 PD patients shows that they use various mental strategies to cope with gait impairments, which can either increase or decrease overall sympathetic tone. This suggests that arousal can have both detrimental and alleviating effects on gait control in PD.
TRANSLATIONAL NEURODEGENERATION
(2023)
Article
Neurosciences
Martin E. Johansson, Nina M. van Lier, Roy P. C. Kessels, Bastiaan R. Bloem, Rick C. Helmich
Summary: Heterogeneity in Parkinson's disease (PD) makes it difficult to understand the disease and develop treatments. Stratifying patients into subtypes based on clinical characteristics may help overcome this challenge. A recent study classified de novo PD patients into three subtypes and found that the diffuse-malignant subtype had more severe symptoms and faster progression compared to the mild-motor predominant subtype. These findings suggest different pathophysiological mechanisms underlie distinct PD subtypes.
NPJ PARKINSONS DISEASE
(2023)
Editorial Material
Neurosciences
Federica Albanese, Bastiaan R. Bloem, Lorraine V. Kalia
Summary: Metascience emphasizes the importance of replication, reproducibility, and rigor in research, particularly in studying major diseases like Parkinson's disease.
JOURNAL OF PARKINSONS DISEASE
(2023)
Review
Clinical Neurology
Carlo Alberto Artusi, Christian Geroin, Jorik Nonnekes, Camila Aquino, Divyani Garg, Marian L. Dale, Darbe Schlosser, Yijie Lai, Mohammad Al-Wardat, Mehri Salari, Robin Wolke, Valery Tsinda Labou, Gabriele Imbalzano, Serena Camozzi, Marcelo Merello, Bastiaan R. Bloem, Tamine Capato, Ruth Djaldetti, Karen Doherty, Alfonso Fasano, Houyam Tibar, Leonardo Lopiano, Nils G. Margraf, Caroline Moreau, Yoshikazu Ugawa, Roongroj Bhidayasiri, Michele Tinazzi
Summary: Axial postural abnormalities are common in patients with Parkinson's disease and atypical parkinsonism, and have a significant impact on the patients' quality of life. However, there is limited understanding of the pathophysiology and clinical predictors of these symptoms, highlighting the need for further research in this area.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Milan Beckers, Peter J. Koehler, Geert J. A. Wanten, Bastiaan R. Bloem
Summary: There is a hypothesis suggesting that Adolf Hitler had Parkinson's disease and suffered from gastrointestinal symptoms, possibly linked to small-intestinal bacterial overgrowth (SIBO), serving as an early indication of Parkinson's.
EUROPEAN NEUROLOGY
(2023)
Letter
Clinical Neurology
Rui Araujo, Jos J. Kole, Joaquim J. Ferreira, Bastiaan R. Bloem
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Francisco Cardoso, Christopher G. Goetz, Tiago A. Mestre, Cristina Sampaio, Charles H. Adler, Daniela Berg, Bastiaan R. Bloem, David J. Burn, Michael S. Fitts, Thomas Gasser, Christine Klein, Marina A. J. de Tijssen, Anthony E. Lang, Shen-Yang Lim, Irene Litvan, Wassilios G. Meissner, Brit Mollenhauer, Njideka Okubadejo, Michael S. Okun, Ronald B. Postuma, Per Svenningsson, Louis C. S. Tan, Taiji Tsunemi, Sarah Wahlstrom-Helgren, Oscar S. Gershanik, Victor S. C. Fung, Claudia Trenkwalder
MOVEMENT DISORDERS
(2023)