Article
Clinical Neurology
Anniina Snellman, Juan Lantero-Rodriguez, Andreja Emersic, Agathe Vrillon, Thomas K. Karikari, Nicholas J. Ashton, Milica Gregoric Kramberger, Sasa Cucnik, Claire Paquet, Uros Rot, Henrik Zetterberg, Kaj Blennow
Summary: The study develops new N-terminal-directed CSF total tau assays, which show increased levels ahead of standard t-tau in the Alzheimer's disease continuum, higher levels in patients with CJD or acute neurological diseases, and better potential as Alzheimer's disease blood biomarkers compared to Quanterix total tau.
Article
Neurosciences
Sook Yoong Chia, Ashwati Vipin, Kok Pin Ng, Haitao Tu, Ananth Bommakanti, Brian Zhiyang Wang, Yi Jayne Tan, Fatin Zahra Zailan, Adeline Su Lyn Ng, Shuo-Chien Ling, Katsutomo Okamura, Eng-King Tan, Nagaendran Kandiah, Li Zeng
Summary: This study aimed to identify a novel blood-based biomarker for dementia of the Alzheimer's type (DAT). The research found that miR-150-5p expression was significantly upregulated in DAT patients and correlated with AD pathology and clinical measures of DAT.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Neurosciences
Amber Nous, Mandy Melissa Jane Wittens, Yannick Vermeiren, Peter Paul De Deyn, Christine Van Broeckhoven, Guy Nagels, Ilse Smolders, Sebastiaan Engelborghs
Summary: This study aimed to evaluate the correlation between serum melatonin levels and spinal CSF melatonin levels in AD. The results showed a positive correlation between daytime serum melatonin levels and spinal CSF melatonin levels in AD patients, but no correlation was found between daytime melatonin levels and changes in cognitive impairment.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Sarah Holper, Rosie Watson, Nawaf Yassi
Summary: The advances in tau detection have revolutionized the diagnosis of neurodegenerative diseases, offering improved diagnostic accuracy and potential as a predictor of clinical progression and drug therapy response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lorenzo Barba, Steffen Halbgebauer, Federico Paolini Paoletti, Giovanni Bellomo, Samir Abu-Rumeileh, Petra Steinacker, Federico Massa, Lucilla Parnetti, Markus Otto
Summary: The expression of SerpinA1 isoforms is altered in patients with Alzheimer's disease (AD) and correlates with core biomarkers of the disease. Analysis of SerpinA1 isoforms shows good diagnostic accuracy in distinguishing AD patients from other neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Karolina Minta, Gunnar Brinkmalm, Erik Portelius, Per Johansson, Johan Svensson, Petronella Kettunen, Anders Wallin, Henrik Zetterberg, Kaj Blennow, Ulf Andreasson
Summary: The study identified that the concentrations of brevican and neurocan peptides were significantly decreased in the cerebrospinal fluid of VaD patients, suggesting their potential as diagnostic biomarkers for VaD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Carmen Lage, Andrea Gonzalez-Suarez, Maria Puerto Alcalde-Hierro, Maria Isabel Sampedro-Gonzalez, Maria Angeles Villanueva-Eguaras, Manuel Ruben Sanchez-Crespo, Catherine Widmann, Frederic Brosseron, Ana Pozueta, Sara Lopez-Garcia, Maria Garcia-Martinez, Martha Kazimierczak, Maria Bravo-Gonzalez, Andrea Fernandez-Rodriguez, Marta Drake-Perez, Juan Irure-Ventura, Marcos Lopez-Hoyos, Eloy Rodriguez-Rodriguez, Michael T. Heneka, Pascual Sanchez-Juan
Summary: Surgery may accelerate memory decline in cognitively asymptomatic individuals with preclinical Alzheimer's disease, especially in those with abnormal levels of amyloid-beta, while the presence of amyloid-beta does not seem to impact the overall incidence of perioperative neurocognitive disorders.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Inmaculada Lopez-Font, Matthew P. Lennol, Guillermo Iborra-Lazaro, Henrik Zetterberg, Kaj Blennow, Javier Saez-Valero
Summary: This study examines the differential effects of reelin proteolytic fragments in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients. The study finds that AD patients have decreased levels of full-length reelin and altered expression levels of different reelin fragments. Additionally, the presence of abnormal reelin species with a molecular mass of around 500 kDa is observed in AD samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Anna Lidia Wojdala, Giovanni Bellomo, Lorenzo Gaetani, Andrea Toja, Elena Chipi, Dandan Shan, Davide Chiasserini, Lucilla Parnetti
Summary: The transition from cerebrospinal fluid (CSF) to plasma provides new avenues for studying molecular phenotypes of Alzheimer's disease (AD). This study evaluated a panel of AD biomarkers in matched CSF and plasma samples, comparing their diagnostic performance and evaluating their trajectories along the AD progression. The findings suggest that a standardized panel of selected plasma markers can facilitate early AD diagnosis and monitoring of disease progression.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Emelie Andersson, Nina Schultz, Takashi Saito, Takaomi C. Saido, Kaj Blennow, Gunnar K. Gouras, Henrik Zetterberg, Oskar Hansson
Summary: This study investigated the relationship between A beta 42/A beta 40 ratios and cerebral A beta pathology using App knock-in mouse models. The results showed a negative association between A beta 42/A beta 40 ratios and cerebral A beta plaque burden in App(NL-F/NL-F) mice, with stronger correlations observed in CSF compared to serum. Additionally, the decline in A beta 42/A beta 40 ratios in CSF and serum occurred after the deposition of A beta aggregates in the brain reached significance. However, no similar changes were observed in App(NL/NL) mice.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Clinical Neurology
Niels Hansen, Berend Malchow, Bianca Teegen, Jens Wiltfang, Claudia Bartels
Summary: This report presents a case of neurochondrin autoimmunity associated with Alzheimer's disease (AD) dementia. The patient exhibited typical clinical and imaging features of AD, including elevated tau and ptau 181 proteins and a reduced Ass42/40 ratio in cerebrospinal fluid (CSF). Neurochondrin autoantibodies were detected in the patient's CSF, expanding the phenotypic spectrum of neurochondrin autoimmunity to include major cognitive disorders such as AD dementia. The onset of AD symptoms in this case may have been accelerated by the neurochondrin autoimmunity via a synergistic or negatively additive hybrid mechanism of action between neurodegeneration and autoimmunity.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Tyler Saunders, Ciaran Gunn, Kaj Blennow, Hlin Kvartsberg, Henrik Zetterberg, Susan D. Shenkin, Simon R. Cox, Ian J. Deary, Colin Smith, Declan King, Tara Spires-Jones
Summary: Neurogranin (Ng), a post-synaptic protein, has been investigated as a biomarker for Alzheimer's disease (AD) and aging in cerebrospinal fluid (CSF). Our study examined Ng abundance in post-mortem human brain tissue in AD, healthy aging (HA), and mid-life (ML) cohorts. Ng levels were quantified using immunohistochemistry in brain regions associated with cognitive change. The results showed significantly reduced Ng levels in AD compared to HA and ML cases, indicating loss of neurogranin in the brain. Our findings support the use of CSF Ng as a biomarker for AD and cognitive decline in healthy aging.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Kyoka Hoshi, Hiromi Ito, Eriko Abe, Takashi J. Fuwa, Mayumi Kanno, Yuta Murakami, Mitsunari Abe, Takenobu Murakami, Akioh Yoshihara, Yoshikazu Ugawa, Takashi Saito, Takaomi C. Saido, Kana Matsumoto, Yoshiki Yamaguchi, Katsutoshi Furukawa, Hiroyuki Arai, Mitsuyasu Kanai, Masakazu Miyajima, Hajime Arai, Norihiro Ogawa, Hiroyasu Akatsu, Yoshio Hashizume, Hiroaki Tateno, Takashi Honda, Yasuhiro Hashimoto
Summary: The study explored glycan-biomarkers on Tf in cerebrospinal fluid, finding that Man-Tf levels were significantly increased in patients with AD and MCI, correlating well with p-tau levels. Man-Tf could be a new biomarker for AD.
Article
Virology
Peter Hermann, Philip Haller, Stefan Goebel, Timothy Bunck, Christian Schmidt, Jens Wiltfang, Inga Zerr
Summary: CSF t-tau is a reliable biomarker for sCJD, but false positive results may occur, especially in rpAD and acute encephalopathies. The t-tau/p-tau ratio may improve the diagnostic accuracy in centers where specific biomarkers are not available.
Article
Neurosciences
Chen Wen, Yan-Lin Bi, Hao Hu, Shu-Yi Huang, Ya-Hui Ma, He-Ying Hu, Lan Tan, Jin-Tai Yu
Summary: The study found that individuals with SCD showed pathophysiological changes in CSF A beta pathology, providing new insights for early intervention of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Isabelle Glans, Emily Sonestedt, Katarina Nagga, Anna-Marta Gustavsson, Esther Gonzalez-Padilla, Yan Borne, Erik Stomrud, Olle Melander, Peter M. Nilsson, Sebastian Palmqvist, Oskar Hansson
Summary: This study aimed to investigate whether adherence to conventional dietary recommendations or to a modified Mediterranean diet are associated with a subsequent lower risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or with future accumulation of AD-related beta-amyloid (A beta) pathology. The results showed that adherence to either conventional dietary recommendations or a modified Mediterranean diet did not significantly lower the risk of developing dementia or AD pathology.
Article
Clinical Neurology
C. Mallinckrodt, Y. Tian, P. S. Aisen, F. Barkhof, S. Cohen, G. Dent, O. Hansson, K. Harrison, T. Iwatsubo, C. J. Mummery, K. K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, C. von Hehn, C. H. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock, T. Chen, S. Budd Haeberlein
Summary: Post-hoc analyses of the EMERGE and ENGAGE studies showed that the outcomes in the high-dose group of ENGAGE were affected by an imbalance in a small number of rapidly progressing patients and lower exposure to the target dose. However, these factors were only present in early enrolled patients and did not affect later enrolled patients. Baseline characteristics and amyloid-related imaging abnormalities did not contribute to the difference in results between the high-dose arms.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Alexandra Koenig, N. Linz, E. Baykara, J. Troeger, C. Ritchie, S. Saunders, S. Teipel, S. Koehler, G. Sanchez-Benavides, O. Grau-Rivera, J. D. Gispert, S. Palmqvist, P. Tideman, O. Hansson
Summary: The study aims to validate speech biomarkers for early identification of Alzheimer's disease (AD) using remote telephone screening and advanced machine learning. By comparing speech data from different risk populations across Europe, novel speech markers can be identified. This research provides a tool for screening individuals at risk of dementia and monitoring them over time.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Tharick A. A. Pascoal, Antoine Leuzy, Joseph Therriault, Mira Chamoun, Firoza Lussier, Cecile Tissot, Olof Strandberg, Sebastian Palmqvist, Erik Stomrud, Pamela C. L. Ferreira, Joao Pedro Ferrari-Souza, Ruben Smith, Andrea Lessa Benedet, Serge Gauthier, Oskar Hansson, Pedro Rosa-Neto
Summary: This study investigates the optimal combination of amyloid-beta/tau/neurodegeneration (A/T/N) biomarkers for the diagnosis of Alzheimer's disease (AD) dementia. The results show that the tau biomarkers perform as well as the complete A/T/N system in diagnosing AD dementia. Additionally, the use of A or T neuroimaging biomarkers alone is equally effective in differentiating AD dementia from non-AD neurodegenerative diseases compared to using the complete A/T/N system.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)
Article
Clinical Neurology
Lei Yu, Patricia A. Boyle, Shorena Janelidze, Vladislav A. Petyuk, Tianhao Wang, David A. Bennett, Oskar Hansson, Julie A. Schneider
Summary: Plasma p-tau217 is a specific biomarker associated with Alzheimer's disease (AD) pathological changes, showing higher accuracy in differentiating AD from primary age-related tauopathy (PART) compared to p-tau181. It is also strongly correlated with brain beta-amyloid and PHFtau tangles. These findings support the potential use of p-tau217 in identifying patients suitable for anti-AD therapies.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Patrick Oeckl, Shorena Janelidze, Steffen Halbgebauer, Erik Stomrud, Sebastian Palmqvist, Markus Otto, Oskar Hansson
Summary: Beta-synuclein can serve as a synaptic blood biomarker for Alzheimer's disease, even in the preclinical stages. Higher levels of plasma beta-synuclein are observed in preclinical AD, mild cognitive impairment, and AD dementia. The levels are associated with amyloid and tau pathology, as well as cognitive impairment and temporal cortical thinning.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Eske Christiane Gertje, Shorena Janelidze, Danielle van Westen, Nicholas Cullen, Erik Stomrud, Sebastian Palmqvist, Oskar Hansson, Niklas Mattsson-Carlgren
Summary: There is an association between white matter lesions (WML) and CSF biomarkers of neuroinflammation in individuals without dementia. Especially, PlGF is associated with WML independent of Aβ status and cognitive impairment.
Article
Clinical Neurology
Philip S. Insel, Atul Kumar, Oskar Hansson, Niklas Mattsson-Carlgren
Summary: This study found that certain genetic variations can modulate the relationship between Aβ and cognitive ability, explaining the heterogeneity in cognitive function in early AD. One specific genetic variant near the ARPP21 gene was associated with cognitive decline and accelerated brain atrophy, potentially identifying individuals at higher risk for AD progression.
Article
Biochemistry & Molecular Biology
Kanta Horie, Gemma Salvado, Nicolas R. Barthelemy, Shorena Janelidze, Yan Li, Yingxin He, Benjamin Saef, Charles D. Chen, Hong Jiang, Olof Strandberg, Alexa Pichet Binette, Sebastian Palmqvist, Chihiro Sato, Pallavi Sachdev, Akihiko Koyama, Brian A. Gordon, Tammie L. S. Benzinger, David M. Holtzman, John C. Morris, Niklas Mattsson-Carlgren, Erik Stomrud, Rik Ossenkoppele, Suzanne E. Schindler, Oskar Hansson, Randall J. Bateman
Summary: Aggregated insoluble tau is a defining feature of Alzheimer's disease, and there is a need for specific fluid biomarkers to track these tau aggregates. However, current fluid biomarkers are not specific enough. Researchers have identified a new cerebrospinal fluid biomarker, MTBR-tau243, which is specific for insoluble tau aggregates and shows strong associations with tau-positron emission tomography and cognitive measures.
Article
Biochemistry & Molecular Biology
Corinne Quadalti, Sebastian Palmqvist, Sara Hall, Marcello Rossi, Angela Mammana, Shorena Janelidze, Sofia Dellavalle, Niklas Mattsson-Carlgren, Simone Baiardi, Erik Stomrud, Oskar Hansson, Piero Parchi
Summary: Prospective and longitudinal analyses of patients with cognitive impairment revealed that the in vivo detection of Lewy body pathology is independently associated with hallucinations, worse attention/executive, visuospatial and motor function, and predicted future cognitive decline. LB pathology has clinical effects in patients with cognitive impairment, especially in those coexisting with AD pathology. LB pathology is associated with faster cognitive decline, regardless of AD pathology and cognitive stage, which suggests that LB status is a better predictor for clinical trajectories than AD biomarkers and clinical diagnosis.
Article
Clinical Neurology
Victor Villemagne, Antoine Leuzy, Sandra Sanabria Bohorquez, Santiago Bullich, Hitoshi C. Shimada, Christopher Rowe, Pierrick Bourgeat, Brian Lopresti, Kun Huang, Natasha Krishnadas, Jurgen Fripp, Yuhei Takado, Alexandra Gogola, Davneet Minhas, Robby Weimer, Makoto Higuchi, Andrew Stephens, Oskar Hansson, Vincent Dore
Summary: This study developed multiple cortical tau tracers and generated a universal scale for cortical tau imaging. This universal scale allows for standardized quantitative measures of tau across different tracers and centers.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)
Article
Cell Biology
Oskar Hansson, Kaj Blennow, Henrik Zetterberg, Jeffrey Dage
Summary: Blood-based biomarkers have the potential to greatly improve the diagnosis and prognosis of Alzheimer's disease (AD) in clinical practice. Assays for measuring phosphorylated tau (p-tau) in plasma have high diagnostic accuracy in distinguishing AD from other neurodegenerative diseases in patients with cognitive impairment. These biomarkers can also predict the future development of AD dementia in patients with mild cognitive complaints. The use of such blood-based biomarkers can reduce the need for more costly investigations and facilitate identification of individuals with pre-symptomatic AD in clinical trials.
Correction
Neurosciences
Luke Harper, Olof Lindberg, Martina Bocchetta, Emily G. Todd, Olof Strandberg, Danielle van Westen, Erik Stomrud, Maria Landqvist WaldO, Lars-Olof Wahlund, Oskar Hansson, Jonathan D. Rohrer, Alexander Santillo
Article
Clinical Neurology
Nicholas C. Cullen, Shorena Janelidze, Erik Stomrud, Randall J. Bateman, Sebastian Palmqvist, Oskar Hansson, Niklas Mattsson-Carlgren
Summary: The use of blood-based biomarkers can reduce screening costs in secondary prevention trials of Alzheimer's disease.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Shorena Janelidze, Nicolas R. Barthelemy, Yingxin He, Randall J. Bateman, Oskar Hansson
Summary: This study found that CKD was associated with increased plasma levels of soluble tau, but the associations with p-tau217 were significantly lower than the association with A beta positivity. Importantly, the ratios, especially pT217/T217, were less associated with CKD than p-tau forms alone, and therefore are likely to more accurately reflect AD-related pathological changes.