Citations 2
TDP-43–Associated Neurodegenerative Disease Conceptualization and Integrated Staging
Benatar, Michael, Lagier‐Tourenne, Clotilde , Gregory, Jenna, Al-Chalabi, Ammar, Boeve, Bradley F., Maragakis, Nicholas J., Wuu, Joanne, Zeier, Zane, Onyike, Chiadi, Lewcock, Joe, Hovinga, Collin, Jafar-nejad, Paymaan, Uspenskaya, Olga, Simmons, Adam, Browne, Susan E., Rohrer, Jonathan, Petrucelli, Leonard, Shapiro, Jacquelyn, Scharper, Deb, Boxer, Adam, Staffaroni, Adam M. , Dacks, Penny, Dave, Kuldip D. , Majo, Martina de, Mitic, Laura, Fradette, Stephanie , Haeberlein, Samantha Budd , Simuni, Tanya, Dunn, Billy, Lee, Edward B., Js, Gregory , Benatar, Michael, Barmada, Sami, Jicha, Gregory A. , Al‐Chalabi, Ammar , Boeve, Bradley F. , Jack, Clifford R. , Seeley, William W. , Maragakis, Nicholas J. , Wuu, Joanne , Zeier, Zane R. , Hovinga, Collin A. , Jafar‐Nejad, Paymaan , Uspenskaya, Olga, Simmons, Adam, Browne, Susan E. , Petrucelli, L, Ostrow, Lyle W. , Dacks, Penny A. , Turner, Martin R. , Majo, Martina de , Simuni, Tanya , McMillan, Corey T. , Lee, Edward B.
JAMA Neurology | August 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Importance Classifying disease based on underlying pathobiology rather than clinical phenotype has implications for the development of biomarkers and therapy development. Observations Transactive response DNA-binding protein 43 kDa (TDP-43) pathology is observed across a range of clinically defined neurodegenerative disorders including limbic predominant age-related encephalopathy (LATE), most cases of amyotrophic lateral sclerosis (ALS), inclusion body myositis, multisystem proteinopathy, and approximately half the cases of frontotemporal dementia (FTD). Despite this shared biology, the current nosology for these neurodegenerative disorders is based on their distinct clinical phenotypes. An alternative approach recognizes the central role of TDP-43 pathology in disease pathogenesis, reserving the use of clinical terms like ALS, FTD, or LATE to describe phenotypic manifestations of underlying pathobiology. This approach also recognizes the converging biomarker and neuropathological data indicating that pathology begins presymptomatically, before the overt clinical manifestations of disease appear. Conclusions and Relevance In proposing a pathobiological definition of disease, the goal is to provide a road map for developing biomarkers that accurately reflect the underlying pathobiology of disease and for advancing therapeutic candidates that effectively target fundamental disease mechanisms.
A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
Jessen, Frank , Amariglio, Rebecca E. , Breteler, Monique M.B. , Ceccaldi, Mathieu , Chételat, Gaël , Dubois, Bruno , Dufouil, Carole , Ellis, Kathryn A. , Flier, Wiesje M. van der , Glodzik, Lidia , Harten, Argonde C. van , Leon, Mony J. de , McHugh, Pauline, Mielke, Michelle M. , Molinuevo, José Luís , Mosconi, Lisa , Osorio, Ricardo S. , Perrotin, Audrey , Petersen, Ronald C. , Rabin, Laura A., Rami, Lorena , Reisberg, Barry , Sachdev, Perminder S. , Sayette, Vincent de La , Saykin, Andrew J. , Scheltens, Philip , Shulman, Melanie , Slavin, Melissa J., Stewart, Robert , Uspenskaya, Olga, Vellas, Bruno , Visser, Pieter Jelle , Wagner, Michael , Group, Subjective Cognitive Decline Initiative (SCD‐I) Working, Boxtel, Martin P.J. van , Rentz, Dorene M. , Sperling, Reisa Anne , Stewart, Robert , Group, Subjective Cognitive Decline Initiative (SCD‐I) Working, Mielke, Michelle M , Saykin, Andrew J , Sachdev, Perminder S , van der Flier, Wiesje M , Scheltens, Philip , Molinuevo, José Luis
Alzheimer's & Dementia | May 3, 2014 | Volume: 10 | Issue: 6 | Pages: 844-852
Abstract There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD‐I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre‐mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus .