Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease.

Autor: Horie K; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.; Eisai Inc., Nutley, NJ.; The Tracy Family SILQ Center, Washington University School of Medicine, St. Louis, MO., Li Y; Department of Neurology, Washington University School of Medicine, Saint Louis, MO., Barthélemy NR; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.; The Tracy Family SILQ Center, Washington University School of Medicine, St. Louis, MO., Gordon B; Department of Radiology, Washington University School of Medicine, St. Louis, MO., Hassenstab J; Department of Neurology, Washington University School of Medicine, Saint Louis, MO., Benzinger TLS; Department of Radiology, Washington University School of Medicine, St. Louis, MO., Fagan AM; Department of Neurology, Washington University School of Medicine, Saint Louis, MO., Morris JC; Department of Neurology, Washington University School of Medicine, Saint Louis, MO., Karch CM; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO., Xiong C; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO., Allegri R; Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) Instituto de Investigaciones Neurológicas Raúl Correa, Buenos Aires, Argentina., Mendez PC; Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) Instituto de Investigaciones Neurológicas Raúl Correa, Buenos Aires, Argentina., Ikeuchi T; Niigata University, Niigata, Japan., Kasuga K; Niigata University, Niigata, Japan., Noble J; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, G.H. Sergievsky Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY., Farlow M; Department of Neurology, Indiana University, Indianapolis, IN., Chhatwal J; Massachusetts General Hospital, Harvard Medical School Boston, Boston, MA., Day G; Department of Neurology, Mayo Clinic in Florida, Jacksonville, FL., Schofield PR; Neuroscience Research Australia, Sydney, New South Wales, Australia.; School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales, Australia., Masters CL; The Florey Institute and the University of Melbourne, Parkville, Victoria, Australia., Levin J; German Center for Neurodegenerative Diseases (DZNE) Munich, Munchen, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany., Jucker M; German Center for Neurodegenerative Diseases (DZNE) Tübingen, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany., Lee JH; Department of Neurology, Asan Medical Center, Seoul, Korea., Roh JH; Departments of Biomedical Sciences, Physiology, and Neurology, Korea University College of Medicine, Seoul, Korea., Sato C; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.; The Tracy Family SILQ Center, Washington University School of Medicine, St. Louis, MO., Sachdev P; Eisai Inc., Nutley, NJ., Koyama A; Eisai Inc., Nutley, NJ., Reyderman L; Eisai Inc., Nutley, NJ., Bateman RJ; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.; The Tracy Family SILQ Center, Washington University School of Medicine, St. Louis, MO., McDade E; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2023 Jun; Vol. 93 (6), pp. 1158-1172. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1002/ana.26620
Abstrakt: Objective: Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR-tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms.
Methods: Cross-sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy.
Results: CSF MTBR-tau species located within the putative "border" region and one species corresponding to the "core" region of aggregates in neurofibrillary tangles (NFTs) increased during the presymptomatic stage and decreased during the symptomatic stage. The "border" MTBR-tau species were associated with amyloid pathology and CSF p-tau; whereas the "core" MTBR-tau species were associated stronger with tau PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFTs.
Interpretation: Changes in CSF soluble MTBR-tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R-specific MTBR-tau (border) to the NFT (core) MTBR-tau species corresponds to the pathology of NFTs in DIAD and change with disease progression. The dynamics between different MTBR-tau species in the CSF may serve as a marker of tau-related disease progression and target engagement of anti-tau therapeutics. ANN NEUROL 2023;93:1158-1172.
(© 2023 American Neurological Association.)
Databáze: MEDLINE
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