Change in cerebrospinal fluid tau microtubule binding region detects symptom onset, cognitive decline, tangles, and atrophy in Dominantly Inherited Alzheimer's Disease
- Authors
- Horie, Kanta; Li, Yan; Barthélemy, Nicolas R.; Gordon, Brian A.; Hassenstab, Jason; Benzinger, Tammie. L.S.; Fagan, Anne M.; Morris, John C.; Karch, Celeste M.; Xiong, Chengjie; Allegri, Ricardo; Mendez, Patricio Chrem; Ikeuchi, Takeshi; Kasuga, Kensaku; Noble, James; Farlow, Martin; Chhatwal, Jasmeer; Day, Gregory S.; Schofield, Peter R.; Masters, Colin L.; Levin, Johannes; Jucker, Mathias; Lee, Jae‐Hong; Roh, Jee Hoon; Sato, Chihiro; Sachdev, Pallavi; Koyama, Akihiko; Reyderman, Larisa; Bateman, Randall J.; McDade, Eric; DIAN
- Issue Date
- Jun-2023
- Publisher
- John Wiley & Sons Inc.
- Citation
- Annals of Neurology, v.93, no.6, pp 1158 - 1172
- Pages
- 15
- Indexed
- SCIE
SCOPUS
- Journal Title
- Annals of Neurology
- Volume
- 93
- Number
- 6
- Start Page
- 1158
- End Page
- 1172
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62521
- DOI
- 10.1002/ana.26620
- ISSN
- 0364-5134
1531-8249
- Abstract
- 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 disease related neurofibrillary tau pathological changes. We examined CSF MTBR-tau species in dominantly inherited Alzheimer disease (DIAD) mutation carriers to assess the association with AD biomarkers and clinical symptoms.
Methods
Cross-sectional and longitudinal CSF from 229 DIAD mutation and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and 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 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; while 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 NFT.
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 NFT 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.
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- Appears in
Collections - 1. Basic Science > Department of Physiology > 1. Journal Articles
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