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19 results on '"Grinberg, L.T."'

1. Non-REM stage 3 sleep disruption across the spectrum of AD severity: from cognitively unimpaired to dementia

Author

Yack, L., primary, Walsh, C.M., additional, Falgàs, N., additional, Pandher, N., additional, Coppola, Q., additional, Song, F., additional, Simon, A.J., additional, Tucker, M., additional, Saloner, R., additional, Casaletto, K., additional, Kramer, J.H., additional, Tempini, M. Gorno, additional, Rosen, H., additional, Rabinovici, G.D., additional, Grinberg, L.T., additional, and Neylan, T.C., additional

Published
2024
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2. Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

Author

Taragano, F.E., Kril, J., Cavalieri, M., Jellinger, K.A., Kovacs, G.G., Engelborghs, S., Lafosse, C., Bertolucci, P.H., Brucki, S., Caramelli, P., de Toledo Ferraz Alves, T.C., Bocti, C., Fulop, T., Hogan, D.B., Hsiung, G.R., Kirk, A., Leach, L., Robillard, A., Sahlas, D.J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R.F., Korczyn, A.D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., Di Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D.V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S.Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A.J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L.S., Ikram, M.K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A.J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E.J., Qiu, C., Viitanen, M., Biessels, G.J., de Leeuw, F.-E., den Heijer, T., Exalto, L.G., Kappelle, L.J., Prins, N.D., Richard, E., Schmand, B., van den Berg, E., van der Flier, W.M., Bilgic, B., Allan, L.M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P.J., Farrant, A., Fish, M., Harkness, K., Ince, P.G., Langhorne, P., Mann, J., Matthews, F.E., Mayer, P., Pendlebury, S.T., Perneczky, R., Peters, R., Smithard, D., Stephan, B.C., Swartz, J.E., Todd, S., Werring, D.J., Wijayasiri, S.N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J.N., Corrada, M.M., Crane, P.K., Diniz, B.S., Etcher, L., Fillit, H., Greenberg, S.M., Grinberg, L.T., Hurt, S.W., Lamar, M., Mielke, M., Ott, B.R., Perry, G., Powers, W.J., Ramos-Estebanez, C., Reed, B., Roberts, R.O., Romero, J.R., Saykin, A.J., Seshadri, S., Silbert, L., Stern, Y., Zarow, C., Skrobot, Olivia A., Black, Sandra E., Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., O'Brien, John, Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, and Kehoe, Patrick G.

Published
2018
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3. The Vascular Impairment of Cognition Classification Consensus Study

Author

Taragano, F.E., Kril, J., Cavalieri, M., Jellinger, K.A., Kovacs, G.G., Engelborghs, S., Lafosse, C., Bertolucci, P.H., Brucki, S., Caramelli, P., de Toledo Ferraz Alves, T.C., Bocti, C., Fulop, T., Hogan, D.B., Hsiung, G.R., Kirk, A., Leach, L., Robillard, A., Sahlas, D.J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R.F., Korczyn, A.D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., DI Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D.V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S.Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A.J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L.S., Ikram, M.K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A.J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E.J., Qiu, C., Viitanen, M., Biessels, G.J., de Leeuw, F.-E., den Heijer, T., Exalto, L.G., Kappelle, L.J., Prins, N.D., Richard, E., Schmand, B., van den Berg, E., van der Flier, W.M., Bilgic, B., Allan, L.M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P.J., Farrant, A., Fish, M., Harkness, K., Ince, P.G., Langhorne, P., Mann, J., Matthews, F.E., Mayer, P., Pendlebury, S.T., Perneczky, R., Peters, R., Smithard, D., Stephan, B.C., Swartz, J.E., Todd, S., Werring, D.J., Wijayasiri, S.N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J.N., Corrada, M.M., Crane, P.K., Diniz, B.S., Etcher, L., Fillit, H., Greenberg, S.M., Grinberg, L.T., Hurt, S.W., Lamar, M., Mielke, M., Ott, B.R., Perry, G., Powers, W.J., Ramos-Estebanez, C., Reed, B., Roberts, R.O., Romero, J.R., Saykin, A.J., Seshadri, S., Silbert, L., Stern, Y., Zarow, C., Skrobot, Olivia A., O'Brien, John, Black, Sandra, Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, and Kehoe, Patrick G.

Published
2017
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4. The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

Author

Singleton, E.H., primary, Pijnenburg, Y.A.L, additional, Gami-Patel, P., additional, Boon, B.D.C., additional, Bouwman, F., additional, Papma, J., additional, Seelaar, H., additional, Scheltens, P., additional, Grinberg, L.T., additional, Spina, S., additional, Nana, A.L., additional, Rabinovici, G.D., additional, Seeley, W.W., additional, Ossenkoppele, R., additional, and Dijkstra, A.A., additional

Published
2021
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5. Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP-43-C pathology

Author

Borghesani, V., Battistella, G., Mandelli, M.L., Welch, A., Weis, E., Younes, K., Neuhaus, J., Grinberg, L.T., Seeley, W. M., Spina, S., Miller, B., Miller, Z., and Gorno-Tempini, M.L.

Subjects
mental disorders
Abstract

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally. Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally). Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions. Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease. Highlights ⍰ Anterior temporal lobe (ATL) degeneration is most often caused by FTLD-TDP-43 type C pathology ⍰ Cases can present with predominantly left (60%) or right (40%) ATL atrophy ⍰ Within ATLs, medial regions are more vulnerable than lateral ones ⍰ The observed spectrum of clinical phenotypes is driven by atrophy lateralization ⍰ Left and right temporal variants of FTD should be considered the same disease

Published
2019
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6. Progress toward standardized diagnosis of vascular cognitive impairment

Author

Skrobot, Olivia A., Black, Sandra E., Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., O'Brien, John, Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, Kehoe, Patrick G., Taragano, F.E., Kril, J., Cavalieri, M., Jellinger, K.A., Kovacs, G.G., Engelborghs, S., Lafosse, C., Bertolucci, P.H., Brucki, S., Caramelli, P., de Toledo Ferraz Alves, T.C., Bocti, C., Fulop, T., Hogan, D.B., Hsiung, G.R., Kirk, A., Leach, L., Robillard, A., Sahlas, D.J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R.F., Korczyn, A.D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., Di Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D.V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S.Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A.J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L.S., Ikram, M.K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A.J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E.J., Qiu, C., Viitanen, M., Biessels, G.J., de Leeuw, F.-E., den Heijer, T., Exalto, L.G., Kappelle, L.J., Prins, N.D., Richard, E., Schmand, B., van den Berg, E., van der Flier, W.M., Bilgic, B., Allan, L.M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P.J., Farrant, A., Fish, M., Harkness, K., Ince, P.G., Langhorne, Peter, Mann, J., Matthews, F.E., Mayer, P., Pendlebury, S.T., Perneczky, R., Peters, R., Smithard, D., Stephan, B.C., Swartz, J.E., Todd, S., Werring, D.J., Wijayasiri, S.N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J.N., Corrada, M.M., Crane, P.K., Diniz, B.S., Etcher, L., Fillit, H., Greenberg, S.M., Grinberg, L.T., Hurt, S.W., Lamar, M., Mielke, M., Ott, B.R., Perry, G., Powers, W.J., Ramos-Estebanez, C., Reed, B., Roberts, R.O., Romero, J.R., Saykin, A.J., Seshadri, S., Silbert, L., Stern, Y., Zarow, C., Epidemiology, Neurology, General Practice, VICCCS Grp, Clinicum, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Department of Physics, HUS Neurocenter, Amsterdam Neuroscience - Neurodegeneration, APH - Personalized Medicine, and APH - Methodology

Subjects
0301 basic medicine, Neurology, Delphi Technique, Epidemiology, Delphi method, Delphi, Vascular dementia, 3124 Neurology and psychiatry, 0302 clinical medicine, SMALL VESSEL DISEASE, Neuropsychological assessment, Stroke, medicine.diagnostic_test, Health Policy, Neuropsychology, CLINICAL-CRITERIA, Brain, Cognition, 3. Good health, ALZHEIMERS-DISEASE, Settore MED/26 - NEUROLOGIA, Psychiatry and Mental health, Vascular cognitive impairment, NINDS-AIREN, ACUTE STROKE, STROKE, Clinical psychology, medicine.medical_specialty, Clinical Neurology, MINI-MENTAL-STATE, Guidelines, ATROPHY, 03 medical and health sciences, Cellular and Molecular Neuroscience, WHITE-MATTER CHANGES, Developmental Neuroscience, Vascular, medicine, Journal Article, Dementia, Humans, Intensive care medicine, business.industry, Dementia, Vascular, 3112 Neurosciences, medicine.disease, Criteria, 030104 developmental biology, consensus, Consensus, Neurology (clinical), Geriatrics and Gerontology, Psychiatry and Mental Health, CEREBRAL-BLOOD-FLOW, Human medicine, business, 030217 neurology & neurosurgery
Abstract

Hanna Jokinen tutkimusryhmän jäsenenä (VICCCS Grp) Introduction: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. Methods: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Results: Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. Discussion: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Published
2018

10. Low brain-derived neurotrophic factor levels in post-mortem brains is associated with sub-syndromic neuropsychiatric symptoms

Author

Nunes, P.V., primary, Nascimento, C.F., additional, Kim, H.K., additional, Andreazza, A., additional, Brentani, H.P., additional, Suemoto, C.K., additional, Leite, R.E.P., additional, Ferretti-Rebustini, R.E.D.L., additional, Pasqualucci, C.A., additional, Nitrini, R., additional, Grinberg, L.T., additional, Young, L.T., additional, Jacob-Filho, W., additional, and Lafer, B., additional

Published
2019
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11. Unrevealing the role of a frontotemporal dementia protein (TDP-43 protein) in bipolar disorder

Author

Nascimento, C., primary, Villela, P. Nunes, additional, Kim, H. Kyunghee, additional, De Oliveira, K., additional, Leite, R.E. Paraizo, additional, Ferretti-Rebustini, R.E.D.L., additional, Grinberg, L.T., additional, Suemoto, C.K., additional, Pasqualucci, C.A., additional, Nitrini, R., additional, Jacob-Filho, W., additional, Brentani, H.P., additional, and Lafer, B., additional

Published
2019
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12. The Vascular Impairment of Cognition Classification Consensus Study

Author

Skrobot, Olivia A., primary, O'Brien, John, additional, Black, Sandra, additional, Chen, Christopher, additional, DeCarli, Charles, additional, Erkinjuntti, Timo, additional, Ford, Gary A., additional, Kalaria, Rajesh N., additional, Pantoni, Leonardo, additional, Pasquier, Florence, additional, Roman, Gustavo C., additional, Wallin, Anders, additional, Sachdev, Perminder, additional, Skoog, Ingmar, additional, Taragano, F.E., additional, Kril, J., additional, Cavalieri, M., additional, Jellinger, K.A., additional, Kovacs, G.G., additional, Engelborghs, S., additional, Lafosse, C., additional, Bertolucci, P.H., additional, Brucki, S., additional, Caramelli, P., additional, Toledo Ferraz Alves, T.C., additional, Bocti, C., additional, Fulop, T., additional, Hogan, D.B., additional, Hsiung, G.R., additional, Kirk, A., additional, Leach, L., additional, Robillard, A., additional, Sahlas, D.J., additional, Guo, Q., additional, Tian, J., additional, Hokkanen, L., additional, Jokinen, H., additional, Benisty, S., additional, Deramecourt, V., additional, Hauw, J., additional, Lenoir, H., additional, Tsatali, M., additional, Tsolaki, M., additional, Sundar, U., additional, Coen, R.F., additional, Korczyn, A.D., additional, Altieri, M., additional, Baldereschi, M., additional, Caltagirone, C., additional, Caravaglios, G., additional, Di Carlo, A., additional, DI Piero, V., additional, Gainotti, G., additional, Galluzzi, S., additional, Logroscino, G., additional, Mecocci, P., additional, Moretti, D.V., additional, Padovani, A., additional, Fukui, T., additional, Ihara, M., additional, Mizuno, T., additional, Kim, S.Y., additional, Akinyemi, R., additional, Baiyewu, O., additional, Ogunniyi, A., additional, Szczudlik, A., additional, Bastos‐Leite, A.J., additional, Firmino, H., additional, Massano, J., additional, Verdelho, A., additional, Kruglov, L.S., additional, Ikram, M.K., additional, Kandiah, N., additional, Arana, E., additional, Barroso‐Ribal, J., additional, Calatayud, T., additional, Cruz‐Jentoft, A.J., additional, López‐Pousa, S., additional, Martinez‐Lage, P., additional, Mataro, M., additional, Börjesson‐Hanson, A., additional, Englund, E., additional, Laukka, E.J., additional, Qiu, C., additional, Viitanen, M., additional, Biessels, G.J., additional, Leeuw, F.‐E., additional, Heijer, T., additional, Exalto, L.G., additional, Kappelle, L.J., additional, Prins, N.D., additional, Richard, E., additional, Schmand, B., additional, Berg, E., additional, Flier, W.M., additional, Bilgic, B., additional, Allan, L.M., additional, Archer, J., additional, Attems, J., additional, Bayer, A., additional, Blackburn, D., additional, Brayne, C., additional, Bullock, R., additional, Connelly, P.J., additional, Farrant, A., additional, Fish, M., additional, Harkness, K., additional, Ince, P.G., additional, Langhorne, P., additional, Mann, J., additional, Matthews, F.E., additional, Mayer, P., additional, Pendlebury, S.T., additional, Perneczky, R., additional, Peters, R., additional, Smithard, D., additional, Stephan, B.C., additional, Swartz, J.E., additional, Todd, S., additional, Werring, D.J., additional, Wijayasiri, S.N., additional, Wilcock, G., additional, Zamboni, G., additional, Au, R., additional, Borson, S., additional, Bozoki, A., additional, Browndyke, J.N., additional, Corrada, M.M., additional, Crane, P.K., additional, Diniz, B.S., additional, Etcher, L., additional, Fillit, H., additional, Greenberg, S.M., additional, Grinberg, L.T., additional, Hurt, S.W., additional, Lamar, M., additional, Mielke, M., additional, Ott, B.R., additional, Perry, G., additional, Powers, W.J., additional, Ramos‐Estebanez, C., additional, Reed, B., additional, Roberts, R.O., additional, Romero, J.R., additional, Saykin, A.J., additional, Seshadri, S., additional, Silbert, L., additional, Stern, Y., additional, Zarow, C., additional, Ben‐Shlomo, Yoav, additional, Passmore, Anthony P., additional, Love, Seth, additional, and Kehoe, Patrick G., additional

Published
2016
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17. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD

Author

Rabinovici, G.D., Rosen, H.J., Alkalay, A., Kornak, J., Furst, A.J., Agarwal, N., Mormino, E.C., O'Neil, J.P., Janabi, M., Karydas, A., Growdon, M.E., Jang, J.Y., Huang, E.J., DeArmond, S.J., Trojanowski, J.Q., Grinberg, L.T., Gorno-Tempini, M.L., Seeley, W.W., Miller, B.L., and Jagust, W.J.

Abstract

To compare the diagnostic performance of PET with the amyloid ligand Pittsburgh compound B (PiB-PET) to fluorodeoxyglucose (FDG-PET) in discriminating between Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD).

Published
2011
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18. Neuropathologic features associated with Alzheimer disease diagnosis

Author

Middleton, L.E., Grinberg, L.T., Miller, B., Kawas, C., and Yaffe, K.

Abstract

To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age.

Published
2011
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19. 4-Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration

Author

Salvatore Spina, Eri Saijo, Allison Kraus, William W. Seeley, Irene Litvan, Marcello Rossi, Gianluigi Zanusso, Adam L. Boxer, Douglas Galasko, Shunsuke Koga, Julio C. Rojas, Piero Parchi, Dennis W. Dickson, Byron Caughey, Lea T. Grinberg, Michael A. Metrick, Bernardino Ghetti, Kathy L. Newell, Saijo E., Metrick M.A., Koga S., Parchi P., Litvan I., Spina S., Boxer A., Rojas J.C., Galasko D., Kraus A., Rossi M., Newell K., Zanusso G., Grinberg L.T., Seeley W.W., Ghetti B., Dickson D.W., and Caughey B.

Subjects
0301 basic medicine, Pathology, Aging, Fluoroimmunoassay, Neurodegenerative, Alzheimer's Disease, Strain, chemistry.chemical_compound, 0302 clinical medicine, Cerebrospinal fluid, Diagnosis, Corticobasal degeneration, Protein Isoforms, Pick's Disease, Frontotemporal lobar degeneration, Orders of magnitude (mass), Frontotemporal Dementia (FTD), Neurological, Biomarker (medicine), Thioflavin, Tauopathy, Diagnosi, Biotechnology, medicine.medical_specialty, Clinical Sciences, tau Proteins, Biology, Sensitivity and Specificity, Article, Pathology and Forensic Medicine, Progressive supranuclear palsy, 03 medical and health sciences, Cellular and Molecular Neuroscience, Rare Diseases, mental disorders, medicine, Acquired Cognitive Impairment, Humans, Neurology & Neurosurgery, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomarker, medicine.disease, Brain Disorders, 030104 developmental biology, chemistry, Dementia, Neurology (clinical), Frontotemporal Lobar Degeneration, Tau, 030217 neurology & neurosurgery, Biomarkers
Abstract

To address the need for more meaningful biomarkers of tauopathies, we have developed an ultrasensitive tau seed amplification assay (4R RT-QuIC) for the 4-repeat (4R) tau aggregates of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and other diseases with 4R tauopathy. The assay detected seeds in 106–109-fold dilutions of 4R tauopathy brain tissue but was orders of magnitude less responsive to brain with other types of tauopathy, such as from Alzheimer’s disease cases. The analytical sensitivity for synthetic 4R tau fibrils was ~ 50fM or 2fg/sample. A novel dimension of this tau RT-QuIC testing was the identification of three disease-associated classes of 4R tau seeds; these classes were revealed by conformational variations in the in vitro amplified tau fibrils as detected by thioflavin T fluorescence amplitudes and FTIR spectroscopy. Tau seeds were detected in postmortem cerebrospinal fluid (CSF) from all neuropathologically confirmed PSP and CBD cases but not in controls. CSF from living subjects had weaker seeding activities; however, mean assay responses for cases clinically diagnosed as PSP and CBD/corticobasal syndrome were significantly higher than those from control cases. Altogether, 4R RT-QuIC provides a practical cell-free method of detecting and subtyping pathologic 4R tau aggregates as biomarkers.

Published
2020

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