المؤلفون: Sexton, Claire E., Bitan, Gal, Bowles, Kathryn R., Brys, Miroslaw, Buée, Luc, Maina, Mahmoud Bukar, Clelland, Claire D., Cohen, Ann D., Crary, John F., Dage, Jeffrey L., Diaz, Kristophe, Frost, Bess, Gan, Li, Goate, Alison M., Golbe, Lawrence I., Hansson, Oskar, Karch, Celeste M., Kolb, Hartmuth C., La Joie, Renaud, Lee, Suzee E., Matallana, Diana, Miller, Bruce L., Onyike, Chiadi U., Quiroz, Yakeel T., Rexach, Jessica E., Rohrer, Jonathan D., Rommel, Amy, Sadri-Vakili, Ghazaleh, Schindler, Suzanne E., Schneider, Julie A., Sperling, Reisa A., Teunissen, Charlotte E., Weninger, Stacie C., Worley, Susan L., Zheng, Hui, Carrillo, Maria C.

المصدر: Alzheimer's and Dementia MultiPark: Multidisciplinary research focused on Parkinson´s disease. 20(3):2240-2261

مصطلحات موضوعية: biomarkers, tau, tau-PET, tauopathies, therapeutics, Samhällsvetenskap, Ekonomi och näringsliv, Företagsekonomi, Social Sciences, Economics and Business, Business Administration

الوصف: INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.

URL الوصول: https://lup.lub.lu.se/record/a2126607-c0f8-467a-8831-142e3cc26966
http://dx.doi.org/10.1002/alz.13533

المؤلفون: Biesbroek, J Matthijs, Coenen, Mirthe, DeCarli, Charles, Fletcher, Evan M, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Chen, Christopher PLH, Dal‐Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, Teunissen, Charlotte E, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Venkatraghavan, Vikram, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Kuijf, Hugo J, Biessels, Geert Jan

المصدر: Alzheimer's & Dementia. 20(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Alzheimer's Disease, Prevention, Dementia, Clinical Research, Acquired Cognitive Impairment, Aging, Neurodegenerative, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurological, Humans, Female, Middle Aged, Aged, Aged, 80 and over, Male, White Matter, Arteriolosclerosis, Amyloid beta-Peptides, Magnetic Resonance Imaging, amyloid pathology, arteriolosclerosis, dementia, lesion pattern, white matter hyperintensities, Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology

الوصف: IntroductionWhite matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.MethodsIndividual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.ResultsVRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/2pn5p09j

المؤلفون: Schindler, Suzanne E.^{Aff1, IDs41582024009775_cor1}, Galasko, Douglas, Pereira, Ana C., Rabinovici, Gil D.^{Aff4, Aff5}, Salloway, Stephen, Suárez-Calvet, Marc, Khachaturian, Ara S., Mielke, Michelle M., Udeh-Momoh, Chi, Weiss, Joan, Batrla, Richard, Bozeat, Sasha, Dwyer, John R., Holzapfel, Drew, Jones, Daryl Rhys, Murray, James F., Partrick, Katherine A., Scholler, Emily, Vradenburg, George^{Aff15, Aff16}, Young, Dylan, Algeciras-Schimnich, Alicia, Aubrecht, Jiri, Braunstein, Joel B., Hendrix, James, Hu, Yan Helen, Mattke, Soeren, Monane, Mark, Reilly, David, Somers, Elizabeth, Teunissen, Charlotte E., Shobin, Eli, Vanderstichele, Hugo, Weiner, Michael W.^{Aff26, Aff27, Aff28, Aff29}, Wilson, David, Hansson, Oskar^{Aff31, Aff32, IDs41582024009775_cor35}

المصدر: Nature Reviews Neurology. 20(7):426-439

المؤلفون: Zeller, Céline J.^{Aff1, Aff2}, Wunderlin, Marina, Wicki, Korian^{Aff1, Aff2}, Teunissen, Charlotte E., Nissen, Christoph^{Aff4, Aff5}, Züst, Marc A.^{Aff1, IDs1135702401195z_cor6}, Klöppel, Stefan

المصدر: GeroScience: Official Journal of the American Aging Association (AGE). :1-16

المؤلفون: Khalil, Michael^{Aff1, IDs4158202400955x_cor1}, Teunissen, Charlotte E., Lehmann, Sylvain, Otto, Markus, Piehl, Fredrik, Ziemssen, Tjalf, Bittner, Stefan, Sormani, Maria Pia^{Aff8, Aff9}, Gattringer, Thomas^{Aff1, Aff10}, Abu-Rumeileh, Samir, Thebault, Simon, Abdelhak, Ahmed, Green, Ari, Benkert, Pascal^{Aff13, Aff14}, Kappos, Ludwig^{Aff13, Aff14}, Comabella, Manuel, Tumani, Hayrettin, Freedman, Mark S., Petzold, Axel^{Aff18, Aff19}, Blennow, Kaj^{Aff20, Aff21, Aff22, Aff23}, Zetterberg, Henrik^{Aff20, Aff21, Aff24, Aff25, Aff26, Aff27}, Leppert, David^{Aff13, Aff14}, Kuhle, Jens^{Aff13, Aff14, IDs4158202400955x_cor23}

المصدر: Nature Reviews Neurology. 20(5):269-287

المؤلفون: Sexton, Claire E, Bitan, Gal, Bowles, Kathryn R, Brys, Miroslaw, Buée, Luc, Maina, Mahmoud Bukar, Clelland, Claire D, Cohen, Ann D, Crary, John F, Dage, Jeffrey L, Diaz, Kristophe, Frost, Bess, Gan, Li, Goate, Alison M, Golbe, Lawrence I, Hansson, Oskar, Karch, Celeste M, Kolb, Hartmuth C, La Joie, Renaud, Lee, Suzee E, Matallana, Diana, Miller, Bruce L, Onyike, Chiadi U, Quiroz, Yakeel T, Rexach, Jessica E, Rohrer, Jonathan D, Rommel, Amy, Sadri‐Vakili, Ghazaleh, Schindler, Suzanne E, Schneider, Julie A, Sperling, Reisa A, Teunissen, Charlotte E, Weninger, Stacie C, Worley, Susan L, Zheng, Hui, Carrillo, Maria C

مصطلحات موضوعية: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurodegenerative, Alzheimer's Disease, Dementia, biomarkers, tau, tau-PET, tauopathies, therapeutics, Geriatrics, Clinical sciences, Biological psychology

الوصف: IntroductionThe pace of innovation has accelerated in virtually every area of tau research in just the past few years.MethodsIn February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation.ResultsRepresenting academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research.DiscussionThe virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/6mb9p96j

المؤلفون: Tijms, Betty M.^{Aff1, Aff2, IDs43587023005507_cor1}, Vromen, Ellen M.^{Aff1, Aff2}, Mjaavatten, Olav, Holstege, Henne^{Aff1, Aff2, Aff4}, Reus, Lianne M.^{Aff1, Aff2, Aff5}, van der Lee, Sven^{Aff1, Aff2, Aff6}, Wesenhagen, Kirsten E. J.^{Aff1, Aff2}, Lorenzini, Luigi^{Aff7, Aff8}, Vermunt, Lisa^{Aff2, Aff9}, Venkatraghavan, Vikram^{Aff1, Aff2}, Tesi, Niccoló^{Aff6, Aff10}, Tomassen, Jori^{Aff1, Aff2}, den Braber, Anouk^{Aff1, Aff2, Aff11}, Goossens, Julie, Vanmechelen, Eugeen, Barkhof, Frederik^{Aff7, Aff13}, Pijnenburg, Yolande A. L.^{Aff1, Aff2}, van der Flier, Wiesje M.^{Aff1, Aff2, Aff14}, Teunissen, Charlotte E.^{Aff2, Aff9}, Berven, Frode S., Visser, Pieter Jelle^{Aff1, Aff2, Aff15, Aff16}

المصدر: Nature Aging. 4(1):33-47

المؤلفون: Coomans, Emma M., Verberk, Inge M.W., Ossenkoppele, Rik, Verfaillie, Sander C.J., Visser, Denise, Gouda, Mariam, Tuncel, Hayel, Wolters, Emma E., Timmers, Tessa, Windhorst, Albert D., Golla, Sandeep S.V., Scheltens, Philip, van der Flier, Wiesje M., van Berckel, Bart N.M., Teunissen, Charlotte E.

المصدر: Journal of Nuclear Medicine MultiPark: Multidisciplinary research focused on Parkinson´s disease. 64(3):437-443

مصطلحات موضوعية: Alzheimer’s disease, plasma pTau181, tau PET, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Neurovetenskaper, Medical and Health Sciences, Basic Medicine, Neurosciences

الوصف: Both plasma tau phosphorylated at threonine-181 (pTau181) and tau PET show potential for detecting Alzheimer’s disease (AD) pathology and predicting clinical progression. In this study, we performed a head-to-head comparison between plasma pTau181 and tau PET along the AD continuum. Methods: We included participants from the Amsterdam Dementia Cohort who underwent 18F-flortaucipir (tau) PET and had a plasma sample biobanked within 12 mo from tau PET. Fifty subjective cognitive decline (SCD) participants (31 Ab-negative and 19 Ab-positive) and 60 Ab-positive participants with mild cognitive impairment (MCI) or dementia due to AD were included. A subset had 2-y longitudinal plasma pTau181 and tau PET available (n 5 40). Longitudinal neuropsychological test data covering 3.2 6 2.7 y from both before and after tau PET were available. Plasma pTau181 and tau PET were compared in their accuracies in discriminating between cognitive stage (MCI/AD vs. SCD) and preclinical Ab status (SCD Ab-positive vs. SCD Ab-negative), their associations with cross-sectional and longitudinal neuropsychological test performance, and their longitudinal changes over time. Results: When discriminating between preclinical Ab status, the area under the curve (AUC) for plasma pTau181 (0.83) and tau PET (entorhinal, 0.87; temporal, 0.85; neocortical, 0.67) were equally high (all DeLong P . 0.05), but tau PET outperformed plasma pTau181 in discriminating MCI/AD from SCD (AUC for plasma pTau181: 0.74; AUCs for tau PET: entorhinal, 0.89; temporal, 0.92; neocortical, 0.89) (all P, 0.01). Overall, tau PET showed stronger associations with cognitive decline and was associated with a wider variety of cognitive tests than plasma pTau181 (plasma pTau181, 20.02 . b, 20.12; tau PET, 20.01 . b, 20.22). Both plasma pTau181 and tau PET increased more steeply over time in MCI/AD than in SCD (P, 0.05), but only tau PET annual changes were associated with cognitive decline. Conclusion: Our results suggest that plasma pTau181 and tau PET perform equally well in identifying Ab pathology but that tau PET better monitors disease stage and clinical progression.

URL الوصول: https://lup.lub.lu.se/record/d4ff520c-7ab2-4eca-856f-9c31ec39a1b0
http://dx.doi.org/10.2967/jnumed.122.264279

المؤلفون: Delvenne, Aurore, Gobom, Johan, Schindler, Suzanne E., Kate, Mara Ten, Reus, Lianne M., Dobricic, Valerija, Tijms, Betty M., Benzinger, Tammie L. S., Cruchaga, Carlos, Teunissen, Charlotte E., Ramakers, Inez, Martinez-Lage, Pablo, Tainta, Mikel, Vandenberghe, Rik, Schaeverbeke, Jolien, Engelborghs, Sebastiaan, Roeck, Ellen De, Popp, Julius, Peyratout, Gwendoline, Tsolaki, Magda, Freund-Levi, Yvonne, 1956, Lovestone, Simon, Streffer, Johannes, Barkhof, Frederik, Bertram, Lars, Blennow, Kaj, Zetterberg, Henrik, Visser, Pieter Jelle, Vos, Stephanie J. B.

المصدر: Alzheimer's & Dementia.

مصطلحات موضوعية: Alzheimer's disease, biomarkers, cerebrospinal fluid, hippocampal volume, neurodegeneration markers, neurofilament light, neurogranin, pathophysiology, proteomics

الوصف: INTRODUCTION: We aimed to unravel the underlying pathophysiology of the neurodegeneration (N) markers neurogranin (Ng), neurofilament light (NfL), and hippocampal volume (HCV), in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics.METHODS: Individuals without dementia were classified as A+ (CSF amyloid beta [Aβ]42), T+ (CSF phosphorylated tau181), and N+ or N- based on Ng, NfL, or HCV separately. CSF proteomics were generated and compared between groups using analysis of covariance.RESULTS: Only a few individuals were A+T+Ng-. A+T+Ng+ and A+T+NfL+ showed different proteomic profiles compared to A+T+Ng- and A+T+NfL-, respectively. Both Ng+ and NfL+ were associated with neuroplasticity, though in opposite directions. Compared to A+T+HCV-, A+T+HCV+ showed few proteomic changes, associated with oxidative stress.DISCUSSION: Different N markers are associated with distinct neurodegenerative processes and should not be equated. N markers may differentially complement disease staging beyond amyloid and tau. Our findings suggest that Ng may not be an optimal N marker, given its low incongruency with tau pathophysiology.HIGHLIGHTS: In Alzheimer's disease, neurogranin (Ng)+, neurofilament light (NfL)+, and hippocampal volume (HCV)+ showed differential protein expression in cerebrospinal fluid. Ng+ and NfL+ were associated with neuroplasticity, although in opposite directions. HCV+ showed few proteomic changes, related to oxidative stress. Neurodegeneration (N) markers may differentially refine disease staging beyond amyloid and tau. Ng might not be an optimal N marker, as it relates more closely to tau.

وصف الملف: print

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-114653
https://doi.org/10.1002/alz.14103

المؤلفون: Wang, Jijing, Guo, Cong, Meng, Zhaowei, Zwan, Marissa D., Chen, Xin, Seelow, Sven, Lundström, Susanna L., Rodin, Sergey, Teunissen, Charlotte E., Zubarev, Roman A.

المصدر: Alzheimer's & Dementia. 19(4):1491-1502

مصطلحات موضوعية: aging, Alzheimer's disease (AD), blood analysis, deamidation, enzyme-linked immunosorbent assay (ELISA), human serum albumin (HSA), in vitro diagnostics, mass spectrometry, protein aggregation

الوصف: Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts protein structures, making them prone to aggregation. Here we strengthened the link between isoAsp and Alzheimer's disease (AD) by novel approaches to isoAsp analysis in human serum albumin (HSA), the most abundant blood protein and a major carrier of amyloid beta (A beta) and phosphorylated tau (p-tau) in blood. We discovered a reduced amount of anti-isoAsp antibodies (P < 0.0001), an elevated isoAsp level in HSA (P < 0.001), more HSA aggregates (P < 0.0001), and increased levels of free A beta (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with A beta and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of A beta and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-512490
https://doi.org/10.1002/alz.12735
https://uu.diva-portal.org/smash/get/diva2:1801009/FULLTEXT01.pdf