Evidence map›Paper›PMID 41000694›Full record

ArticlebioRxiv : the preprint server for biology2025

CNS-Tau Specific Antibodies Illuminate Disease Signatures Across Tauopathies.

Lei Liu, Yin Zheng, Luke Slominski, Qimin Quan, Adriana Saba, Jean-Pierre Bellier, Han-Bin Yoo, Andrea Roman, Elizabeth L Hennessey, Samadhi P Wijethunga and 5 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Lei LiuBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.ORCID 0000-0002-4604-4629
Yin ZhengBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Luke SlominskiNanoMosaic, LLC., 600 Winter St, Waltham, MA 02451 USA.
Qimin QuanNanoMosaic, LLC., 600 Winter St, Waltham, MA 02451 USA.
Adriana SabaBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Jean-Pierre BellierBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Han-Bin YooBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Andrea RomanBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Elizabeth L HennesseyBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Samadhi P WijethungaBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Elif L OkyayBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Michael B MillerBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.ORCID 0000-0002-6205-3314
Hyun-Sik YangBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.ORCID 0000-0002-8318-0443
Dennis J SelkoeBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Jasmeer P ChhatwalBrigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.ORCID 0000-0002-7792-1698

Funding

Leveraging Heterogeneity in Autosomal Dominant AD to Elucidate Pathophysiology and Improve AD BiomarkersRF1AG079569 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI CHHATWAL, JASMEER P, LIU, LEI · 2022 to 2022
$4.4M
Plasma tau and neurodegenerative markers as predictors of rate of AD progressionR01AG071865 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI CHHATWAL, JASMEER P · 2021 to 2025
$4.2M
Illuminating neurodegenerative tauopathy from somatic genomic landscapes of single human brain cellsDP2AG086138 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Michael B Miller · 2023 to 2026
$2.7M
Mechanisms of Somatic Mutation in Alzheimer's Disease Using Single Neuron AnalysisR01AG082346 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Michael B Miller · 2024 to 2026
$2.7M
NIA NIH HHS DP2 AG086138NIA NIH HHS R01 AG071865NIA NIH HHS R01 AG082346NIA NIH HHS RF1 AG079569
6 · The paper itself

Abstract

Background: Alternative splicing of the MAPT gene produces distinct tau isoforms in the central and peripheral nervous systems (CNS and PNS), yet their respective biological and pathological roles remain poorly understood. Recent studies suggest that CNS-tau may play a key role in amyloid-β associated neurodegeneration in Alzheimer's disease (AD), but the absence of isoform-specific tools has limited both mechanistic insight and biomarker development. We aimed to develop and validate CNS-tau-specific monoclonal antibodies and assess their utility in neuropathology and fluid-based biomarker assays across AD and primary tauopathies. Methods: We generated six recombinant rabbit monoclonal antibodies targeting a CNS-tau-specific sequence encoded by exons 4 and 5. Specificity and affinity were evaluated via biolayer interferometry, immunoblotting, and tau-expressing HEK293 models. The lead clone, LL-T-1-1, was tested in postmortem brain sections from AD (n = 23), progressive supranuclear palsy (PSP, n = 3), and corticobasal degeneration (CBD, n = 3). A second clone, LL-T-1-5, was optimized for use in plasma assays via an ultrasensitive nanoneedle platform, LoD < 1 pg/ml. Results: LL-T-1-1 showed nanomolar affinity for CNS-tau and no cross-reactivity with PNS-tau. It selectively labeled dystrophic neurites in AD and all hallmark tau lesions in PSP and CBD without antigen retrieval. LL-T-1-5-based plasma assays revealed CNS-tau levels significantly correlated with cognitive scores (MMSE and QDRS) and differentiated impaired from unimpaired individuals. Conclusions: CNS-tau-specific antibodies LL-T-1-1 and LL-T-1-5 provide new tools for neuropathology and fluid biomarker development across tauopathies.

Indexed as

Alzheimer’s diseaseCNS-specific tau isoformneurodegenerative disease

Identifiers

PMID41000694
PMCPMC12458136

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.