Review
Chemistry, Analytical
Arezoo Mirzaie, Hassan Nasrollahpour, Balal Khalilzadeh, Ali Akbar Jamali, Raymond J. Spiteri, Hadi Youse, Ibrahim Isildak, Reza Rahbarghazi
Summary: Alzheimer's disease is a prevalent neurodegenerative disorder characterized by progressive deterioration, loss of neurons, and cognitive decline. Amyloid beta and Tau proteins are key biomarkers of the disease, and their abnormal levels in biofluids, particularly cerebrospinal fluid, are directly linked to the incidence and progression of Alzheimer's. Developing sensitive and reliable methods for screening and evaluating these biomarkers in cerebrospinal fluid can aid in early diagnosis and treatment. This article discusses the impact of Alzheimer's on cerebrospinal fluid and provides an overview of the latest biosensors for detecting amyloid beta and Tau in cerebrospinal fluid samples.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Review
Medicine, General & Internal
Efstratios-Stylianos Pyrgelis, Fotini Boufidou, Vasilios C. C. Constantinides, Myrto Papaioannou, Sokratis G. G. Papageorgiou, Leonidas Stefanis, George P. P. Paraskevas, Elisabeth Kapaki
Summary: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological syndrome characterized by gait disorder, cognitive impairment, and urinary incontinence. CSF biomarker studies show differences in concentration of A beta 42 and tau proteins (t-tau and p-tau) between iNPH patients, healthy individuals, and patients with AD and vascular dementia. This could be helpful for diagnosis and prognosis of iNPH.
Article
Medical Laboratory Technology
Anders Abildgaard, Tina Parkner, Cindy Soendersoe Knudsen, Hanne Gottrup, Henriette Klit
Summary: This study found that tau/Aβ 42 ratios have the best diagnostic performance, but the estimated cut-off values for the ratios were slightly higher than previously reported. Therefore, adjustment of the cut-offs may be warranted when using CSF analysis to support a diagnosis of AD in a heterogeneous high-prevalence cohort.
CLINICA CHIMICA ACTA
(2023)
Article
Medicine, General & Internal
Tyler S. Saunders, Natalie Jenkins, Kaj Blennow, Craig Ritchie, Graciela Muniz-Terrera
Summary: The relationship between APOE status and CSF p-tau may be mediated by the interaction between sex and cerebrospinal fluid Al3. These findings suggest that tau accumulation may be independent of Al3 in females, but not in males.
Article
Neurosciences
Soyeon Kim, Kiwon Kim, Kwangsik Nho, Woojae Myung, Hong-Hee Won
Summary: The study found a causal association between CSF biomarkers and the risk of LOAD, suggesting that the etiology of LOAD involves pathways of A beta and tau proteins. Further MR studies using large-scale data are needed to elucidate the pathophysiology of LOAD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Ris E. Jansen, Sven J. van der Lee, Duber Gomez-Fonseca, Itziar de Rojas, Maria Carolina Dalmasso, Benjamin Grenier-Boley, Anna Zettergren, Aniket Mishra, Muhammad Ali, Victor Andrade, Celine Bellenguez, Luca Kleineidam, Fahri Kucukali, Yun Ju Sung, Niccolo Tesi, Ellen M. Vromen, Douglas P. Wightman, Daniel Alcolea, Montserrat Alegret, Ignacio Alvarez, Philippe Amouyel, Lavinia Athanasiu, Shahram Bahrami, Henri Bailly, Olivia Belbin, Sverre Bergh, Lars Bertram, Geert Jan Biessels, Kaj Blennow, Rafael Blesa, Merce Boada, Anne Boland, Katharina Buerger, Angel Carracedo, Laura Cervera-Carles, Genevieve Chene, Jurgen A. H. R. Claassen, Stephanie Debette, Jean-Francois Deleuze, Peter Paul de Deyn, Janine Diehl-Schmid, Srdjan Djurovic, Oriol Dols-Icardo, Carole Dufouil, Emmanuelle Duron, Emrah Duezel, Tormod Fladby, Juan Fortea, Lutz Froelich, Pablo Garcia-Gonzalez, Maria Garcia-Martinez, Ina Giegling, Oliver Goldhardt, Johan Gobom, Timo Grimmer, Annakaisa Haapasalo, Harald Hampel, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Seppo Helisalmi, Michael T. Heneka, Isabel Hernandez, Sanna-Kaisa Herukka, Henne Holstege, Jonas Jarholm, Silke Kern, Anne-Brita Knapskog, Anne M. Koivisto, Johannes Kornhuber, Teemu Kuulasmaa, Carmen Lage, Christoph Laske, Ville Leinonen, Piotr Lewczuk, Alberto Lleo, Adolfo Lopez de Munain, Sara Lopez-Garcia, Wolfgang Maier, Marta Marquie, Merel O. Mol, Laura Montrreal, Fermin Moreno, Sonia Moreno-Grau, Gael Nicolas, Markus M. Nothen, Adelina Orellana, Lene Palhaugen, Janne M. Papma, Florence Pasquier, Robert Perneczky, Oliver Peters, Yolande A. L. Pijnenburg, Julius Popp, Danielle Posthuma, Ana Pozueta, Josef Priller, Raquel Puerta, Ines Quintela, Inez Ramakers, Eloy Rodriguez-Rodriguez, Dan Rujescu, Ingvild Saltvedt, Pascual Sanchez-Juan, Philip Scheltens, Norbert Scherbaum, Matthias Schmid, Anja Schneider, Geir Selbaek, Per Selnes, Alexey Shadrin, Ingmar Skoog, Hilkka Soininen, Lluis Tarraga, Stefan Teipel, Betty Tijms, Magda Tsolaki, Christine Van Broeckhoven, Jasper Van Dongen, John C. van Swieten, Rik Vandenberghe, Jean-Sebastien Vidal, Pieter J. Visser, Jonathan Vogelgsang, Margda Waern, Michael Wagner, Jens Wiltfang, Mandy M. J. Wittens, Henrik Zetterberg, Miren Zulaica, Cornelia M. van Duijn, Maria Bjerke, Sebastiaan Engelborghs, Frank Jessen, Charlotte E. Teunissen, Pau Pastor, Mikko Hiltunen, Martin Ingelsson, Ole A. Andreassen, Jordi Clarimon, Kristel Sleegers, Agustin Ruiz, Alfredo Ramirez, Carlos Cruchaga, Jean-Charles Lambert, Wiesje van der Flier
Summary: This study found that levels of A beta 42 and pTau in cerebrospinal fluid are more direct indicators of the pathogenesis of Alzheimer's disease than clinical diagnosis. Through a collaborative effort, novel associations with AD risk loci and multiple biological pathways related to A beta 42 and pTau were identified.
ACTA NEUROPATHOLOGICA
(2022)
Article
Biochemistry & Molecular Biology
Ioanna Tsantzali, Fotini Boufidou, Eleni Sideri, Antonis Mavromatos, Myrto G. Papaioannou, Aikaterini Foska, Ioannis Tollos, Sotirios G. Paraskevas, Anastasios Bonakis, Konstantinos I. Voumvourakis, Georgios Tsivgoulis, Elisabeth Kapaki, George P. Paraskevas
Summary: Analysis of classical cerebrospinal fluid biomarkers, especially in the context of a diagnostic system like AT(N), can be a significant tool for diagnosing Alzheimer's disease accurately during a patient's lifetime. Despite atypical clinical presentations, the classical biomarker profile was consistent with Alzheimer's disease in four patients, demonstrating the potential usefulness of these biomarkers for identifying the biochemical fingerprints of the disease.
Review
Neurosciences
Donovan A. McGrowder, Fabian Miller, Kurt Vaz, Chukwuemeka Nwokocha, Cameil Wilson-Clarke, Melisa Anderson-Cross, Jabari Brown, Lennox Anderson-Jackson, Lowen Williams, Lyndon Latore, Rory Thompson, Ruby Alexander-Lindo
Summary: This review presents the current evidence on CSF biomarkers for Alzheimer's disease, emphasizing the efficacy of existing core biomarkers and the need for further development of biomarkers reflecting other aspects of the disease mechanism. It also introduces new biomarkers that track Alzheimer's disease pathology and their potential in diagnosis and predicting cognitive decline.
Article
Clinical Neurology
Timo Jan Oberstein, Manuel Alexander Schmidt, Anna Florvaag, Anna-Lena Haas, Eva-Maria Siegmann, Pauline Olm, Janine Utz, Philipp Spitzer, Arnd Doerfler, Piotr Lewczuk, Johannes Kornhuber, Juan Manuel Maler
Summary: In a long-term observational study, it was found that the combination of biomarkers pTau181, A beta 40 and A beta 42 in cerebrospinal fluid (CSF) is not associated with dementia. Individuals with increased levels of CSF-pTau181 without amyloidopathy showed no significant cognitive decline compared to controls.
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)
Article
Medical Laboratory Technology
Rosa Ferrer, Nuole Zhu, Javier Arranz, Inmaculada Porcel, Shaimaa El Bounasri, Oriol Sanchez, Soraya Torres, Josep Julve, Alberto Lleo, Francisco Blanco-Vaca, Daniel Alcolea, Mireia Tondo
Summary: This study aimed to investigate the potential influence of different storage conditions on the quantification of biomarkers related to Alzheimer's disease in cerebrospinal fluid. The results showed that temperature and storage days significantly impacted the concentrations of certain biomarkers. However, the use of a ratio between two biomarkers could partially compensate for this influence. Other biomarkers were not affected by the tested storage conditions. The findings suggest that specific correction factors can be applied for samples stored at 4 degrees C.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2022)
Article
Medicine, General & Internal
Nicholas J. Ashton, Andrea L. Benedet, Tharick A. Pascoal, Thomas K. Karikari, Juan Lantero-Rodriguez, Wagner S. Brum, Sulantha Mathotaarachchi, Joseph Therriault, Melissa Savard, Mira Chamoun, Erik Stoops, Cindy Francois, Eugeen Vanmechelen, Serge Gauthier, Eduardo R. Zimmer, Henrik Zetterberg, Kaj Blennow, Pedro Rosa-Neto
Summary: CSF p-tau epitopes increase early in the development of AD pathology and are a primary candidate for detecting incipient Aβ pathology.
Article
Clinical Neurology
Fardin Nabizadeh, Kasra Pirahesh, Parya Valizadeh
Summary: The study found that the changes in CSF alpha-syn, t-tau, and p-tau were not significant enough to distinguish PD patients with and without RBD. However, CSF A beta 1-42 decreased in the short term and showed a significant difference after a while in PD patients with and without RBD.
JOURNAL OF NEUROLOGY
(2022)
Article
Medicine, General & Internal
George P. P. Paraskevas, Vasilios C. C. Constantinides, Fotini Boufidou, Ioanna Tsantzali, Efstratios-Stylianos Pyrgelis, Georgios Liakakis, Elisabeth Kapaki
Summary: In addition to typical symptoms, Alzheimer's disease (AD) can also present with atypical clinical manifestations. A study of patients with AD cerebrospinal fluid (CSF) biomarker profile found that 46% had typical symptoms, while 23.5% had mixed presentations and 15.3% had atypical presentations. Some of these atypical presentations may need to be included in diagnostic criteria.
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
Benjamin J. Kim, Murray Grossman, Tomas S. Aleman, Delu Song, Katheryn A. Q. Cousins, Corey T. McMillan, Adrienne Saludades, Yinxi Yu, Edward B. Lee, David Wolk, Vivianna M. Van Deerlin, Leslie M. Shaw, Gui-Shuang Ying, David J. Irwin
Summary: Photoreceptor outer nuclear layer (ONL) thinning can distinguish frontotemporal lobar degeneration tauopathy (FTLD-Tau) from Alzheimer's disease (AD) and correlates with disease severity in FTLD-Tau.
NEUROBIOLOGY OF AGING
(2023)
Article
Clinical Neurology
Thomas F. Tropea, Teresa Waligorska, Sharon X. Xie, Ilya M. Nasrallah, Katheryn A. Q. Cousins, John Q. Trojanowski, Murray Grossman, David J. Irwin, Daniel Weintraub, Edward B. Lee, David A. Wolk, Alice S. Chen-Plotkin, Leslie M. Shaw
Summary: The objective of this study was to determine if plasma tau phosphorylated at threonine 181 (p-tau181) can distinguish Alzheimer's disease (AD) from normal cognition (NC) in adults, predict cognitive and functional decline, and validate findings in an external cohort. The results showed that plasma p-tau181 can accurately differentiate AD pathology from NC, and higher levels of p-tau181 are associated with faster cognitive and functional decline.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
Article
Clinical Neurology
Danielle S. Abraham, Thanh Phuong Pham Nguyen, Leah J. Blank, Dylan Thibault, Shelly L. Gray, Sean Hennessy, Charles E. Leonard, Daniel Weintraub, Allison W. Willis
Summary: This study examined the differential prescribing patterns between new and established treatments for common neurological conditions. Using data from a national sample of US commercially insured adults from 2005-2019, the study compared new users of recently approved medications for three conditions: diabetic peripheral neuropathy, Parkinson disease psychosis, and epilepsy. The results showed that newer medications were more frequently prescribed to individuals with prior treatment, suggesting potential bias in comparative effectiveness and safety studies. The study emphasizes the importance of reporting propensity score non-overlap in comparative studies involving newer medications and suggests methodological approaches to address channeling bias.
Review
Clinical Neurology
David G. Coughlin, David J. Irwin
Summary: Several advances have been made in fluid and tissue-based biomarkers for Parkinson's disease (PD) and other synucleinopathies in the last few years. Immunohistochemistry, immunofluorescence, and alpha-synuclein seeding amplification assays now offer a crucial advancement in identifying different species of alpha-synuclein in PD patients. Co-pathology of Alzheimer's disease (AD) is commonly found in PD and dementia with Lewy bodies (DLB), and biofluid biomarkers for tau and amyloid beta species can detect this co-pathology.
Article
Clinical Neurology
Katheryn A. Q. Cousins, David J. Irwin, Alice Chen-Plotkin, Leslie M. Shaw, Sanaz Arezoumandan, Edward B. Lee, David A. Wolk, Daniel Weintraub, Meredith Spindler, Andres Deik, Murray Grossman, Thomas F. Tropea
Summary: This study found that plasma GFAP may be sensitive to concomitant AD pathology in LBSD, especially accumulation of beta-amyloid plaques.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Neurosciences
Kalpana M. Merchant, Tanya Simuni, Janel Fedler, Chelsea Caspell-Garcia, Michael Brumm, Kelly N. H. Nudelman, Elizabeth Tengstrandt, Frank Hsieh, Roy N. Alcalay, Christopher Coffey, Lana Chahine, Tatiana Foroud, Andrew Singleton, Daniel Weintraub, Samantha Hutten, Todd Sherer, Brit Mollenhauer, Andrew Siderowf, Caroline Tanner, Ken Marek
Summary: We quantified concentrations of three isoforms of BMP in different cohorts of Parkinson's disease patients and found that LRRK2 and GBA1 gene mutations were associated with elevated BMP levels. However, BMP is not a prognostic or disease progression biomarker.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Caroline A. McHutchison, Joanne Wuu, Corey T. McMillan, Rosa Rademakers, Jeffrey Statland, Gang Wu, Evadnie Rampersaud, Jason Myers, Jessica P. Hernandez, Sharon Abrahams, Michael Benatar, CReATe Consortium
Summary: In this study, researchers explored the cognitive and behavioral changes in people with motor neuron disease (MND) over time. They found that cognitive impairment was less common than previously reported and remained stable for most participants. However, a small subset of participants experienced a decline in cognition over time, which was not solely related to the C9ORF72 genetic mutation. These findings raise questions about the timing and progression of cognitive impairment in MND.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Daniel Weintraub
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Hubert H. Fernandez, Daniel Weintraub, Eric Macklin, Irene Litvan, Michael A. Schwarzschild, Jamie Eberling, Aleksandar Videnovic, Christopher J. Kenney
Summary: In patients with Parkinson disease dementia (PDD), SYN120 did not improve cognition significantly but showed potential benefits in cognitive activities of daily living and apathy.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Thanh Phuong Pham Nguyen, Shelly L. Gray, Craig W. Newcomb, Qing Liu, Ali G. Hamedani, Daniel Weintraub, Sean Hennessy, Allison W. Willis
Summary: This study found that there were no significant differences in medication prescriptions between Parkinson disease (PD) patients hospitalized for serious injury and those hospitalized for other reasons, indicating a missed opportunity to deprescribe high-risk medications during care transitions.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Multidisciplinary Sciences
Isabel Yannatos, Shana Stites, Rebecca Brown, Corey McMillan
Summary: Racial disparities in aging-related health outcomes among older Americans, known as weathering, are influenced by individual socioeconomic status, neighborhood social environment, and air pollution exposures. Black individuals have significantly accelerated DNA methylation (DNAm) aging compared to White individuals. Socioeconomic status and neighborhood deprivation contribute to the disparity in DNAm aging, while fine particulate matter exposure may also play a role for Black individuals. DNAm aging may contribute to age-related health disparities between older Black and White Americans.