Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease.
The 2 matches
- [1] § Methods › Image Analysis ↔ src/Colocalisation_analysis/2_count_spots.py, lines 102–132 · score 0.59 · localized spots, detected spots, ComDet, channel, threshold
- [2] § Methods › Image Analysis ↔ src/SR_analysis/SR_image_reconstruction.py, lines 1–20 · score 0.50 · Picasso functionality, rendered, precision, reconstructed, Super
Paper
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The authors' code
Python · 149 lines · 5.1 KB · MIT · 1 match
- import functools
- import os
- import matplotlib.pyplot as plt
- import numpy as np
- import pandas as pd
- import seaborn as sns
- from skimage import io
- from loguru import logger
- from smma.src.utilities import comdet
- import smma.src.utilities as utilities
- logger.info('Import OK')
- # Remember to add napari.run() calls after each loop!
- # SETTINGS.application.ipy_interactive = False
- np.set_printoptions(suppress=True) # stop scientific notion for printing
- image_id = ''
- input_folder = utilities.locate_raw_drive_files(input_path='raw_data/raw_data.txt')
- image_folder = f'{input_folder}/{image_id}/'
- input_path = 'results/spot_detection/initial_cleanup/slide_parameters.csv'
- output_folder = 'results/spot_detection/count_spots/'
- control_image = ''
- test_image = ''
- if not os.path.exists(output_folder):
- os.makedirs(output_folder)
- # Read in file directory
- slide_params = pd.read_csv(f'{input_path}')
- slide_params.drop([col for col in slide_params.columns.tolist()
- if 'Unnamed: ' in col], axis=1, inplace=True)
- # remove discard images
- slide_params.dropna(subset=['keep'], inplace=True)
- # ----------Determine optimal parameters----------
- #Generate projection image - in this case, maximum
- max_pixels = 10
- max_threshold = 20
- control_spots = []
- for image_name in [control_image, test_image]:
- image = io.imread(
- f'{image_folder}{image_name}.tif')
- mean_image = np.mean(image, axis=0)
- for pixel_size in range(2, max_pixels+1):
- for threshold in range(3, max_threshold+1):
- visualise = False if threshold == 18 else False
- measurements = comdet(image=mean_image.astype(
- float), sigma_threshold=threshold, particle_guess=pixel_size, visualise=visualise)
- logger.info(f'{len(measurements)} spots detected in {control_image} with particle guess {pixel_size} and threshold {threshold}')
- measurements['particle_guess'] = pixel_size
- measurements['sigma_threshold'] = threshold
- measurements['image_name'] = image_name
- control_spots.append(measurements)
- spots = pd.concat(control_spots)
- spots_per_fov = spots.groupby(['particle_guess', 'sigma_threshold', 'image_name']).count(
- )['label'].reset_index().rename(columns={'label': 'spots_count'})
- fig, axes = plt.subplots(1, 2, figsize=(10, 5))
- for x, image_name in enumerate([control_image, test_image]):
- sns.lineplot(
- data=spots_per_fov[spots_per_fov['image_name'] == image_name],
- x='sigma_threshold',
- y='spots_count',
- hue='particle_guess',
- ax=axes[x]
- )
- axes[x].set_title(image_name)
- plt.tight_layout()
- plt.show()
- comparison = pd.pivot(spots_per_fov, index=['particle_guess', 'sigma_threshold'], columns=['image_name'], values='spots_count').reset_index()
- comparison['proportion'] = comparison[control_image] / comparison[test_image]
- fig, ax = plt.subplots()
- sns.lineplot(
- data=comparison,
- x='sigma_threshold',
- y='proportion',
- hue='particle_guess',
- palette='tab10'
- )
- sns.scatterplot(
- data=comparison[comparison['proportion'] < 0.1].sort_values('sigma_threshold').drop_duplicates(subset=['particle_guess']),
- x='sigma_threshold',
- y='proportion',
- hue='particle_guess',
- palette='tab10'
- )
- plt.legend(bbox_to_anchor=(1.0, 1.0))
- plt.tight_layout()
- plt.show()
- # -----------------localize_spots-----------------
- thresholds = {
- '641': [8, 4],
- '488': [5, 4],
- }
- slide_details = dict()
- # Detect spots
- spots = []
- for x, (layout, image_path, slide_name) in enumerate(slide_params[['layout', 'file_path', 'well_info']].values):
- channel = slide_name.split('_')[-1]
- sigma_threshold, particle_guess = thresholds[channel]
- # Generate projection image - in this case, maximum
- image = io.imread(image_path)
- mean_image = np.mean(image[10:, :, :], axis=0)
- visualise = f'{output_folder}{slide_name}_spots.png' if x % 16 == 0 else False
- measurements = comdet(image=mean_image.astype(
- float), sigma_threshold=sigma_threshold, particle_guess=particle_guess, visualise=visualise)
- logger.info(f'{len(measurements)} spots detected in {slide_name}')
- measurements['layout'] = layout
- measurements['well_info'] = slide_name
- measurements['file_path'] = image_path
- spots.append(measurements)
- spots = pd.concat(spots)
- spots_per_fov = spots.groupby(['file_path', 'well_info', 'layout']).count(
- )['label'].reset_index().rename(columns={'label': 'spots_count'})
- # Add sample info
- spots_per_fov = functools.reduce(lambda left, right: pd.merge(
- left, right, on=['file_path', 'well_info', 'layout'], how='outer'), [slide_params, spots_per_fov])
- # Save to csv
- spots_per_fov.to_csv(f'{output_folder}spots_per_fov.csv')
- spots.to_csv(f'{output_folder}compiled_spots.csv')
- # Add sample info
- spot_stats = spots.groupby(['file_path', 'well_info', 'layout']).mean(
- ).reset_index()
- spot_stats = functools.reduce(lambda left, right: pd.merge(
- left, right, on=['file_path', 'well_info', 'layout'], how='outer'), [slide_params, spot_stats])
- spot_stats.drop([col for col in spot_stats.columns.tolist() if 'Unnamed: ' in col], axis=1, inplace=True)
- spot_stats.to_csv(f'{output_folder}compiled_stats.csv')
2_count_spots.py at commit 44a90a7, under MIT · at the source
Overview
- Yusuf Hamied Department of Chemistry University of Cambridge Cambridge UK
- UK Dementia Research Institute University of Cambridge Cambridge UK
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute King's College London London UK
- Centre For Neuroscience, Surgery and Trauma, The Blizard Institute Queen Mary University of London London UK
- Department of Clinical Neurosciences University of Cambridge Cambridge UK
- Molecular Horizons, School of Sciences University of Wollongong Wollongong New South Wales Australia
Abstract
Tau aggregation is a central pathological feature of Alzheimer's disease, yet how different forms of tau—ranging from monomers to small soluble aggregates and mature fibrils—interact with the cellular environment remains poorly understood. Here, we combine immunoaffinity proteomics with single‐molecule techniques and super‐resolution microscopy to systematically map the tau interactome across defined aggregation states, spanning monomeric tau, nanoscopic soluble aggregates, and fibrillar species. Using post‐mortem Alzheimer's disease brain tissue, we identify distinct functional modules associated with different aggregation states: while proteostasis factors and immune‐related proteins preferentially associate with nanoscopic aggregates (oligomers), cytoskeletal, metabolic, and RNA‐binding proteins are enriched for mature fibrillar tau. Single‐molecule microscopy directly confirms this conformation‐dependent recruitment for key interactors including Hsp70‐2, ENO1, hnRNPA1, APP, EAAT4, and ubiquitin. A primary‐neuron system with accelerated tau aggregation is used to model these findings in a controlled system, showing striking similarities to the brain samples. Finally, pseudotime analysis reconstructs a progressive remodelling of the tau interactome across disease progression, revealing stage‐specific pathway vulnerabilities. Together, these results establish a temporally resolved framework for tau pathology shaped by protein interactions and identify potential therapeutic intervention points for investigation across stages of disease.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repositories
Its files are read in the Code ↔ Paper reader above, with 2 matches between paragraphs and lines of code.
Zenodo 17990783
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
- 26 September 2026: the link answers (HTTP 200)
dboeken/boeken_tau_aggregate_interactome
44a90a7dd6f13b813f20666faa896d156f765e32, 15 May 2026Availability: 1 check, the latest on 26 September 2026: the link answers
- 26 September 2026: the link answers
19 files
- src/
Colocalisation_analysis/ — Python, 66 lines1_initial_cleanup.py - src/
Colocalisation_analysis/ — Python, 149 lines, 1 match2_count_spots.py - src/
Colocalisation_analysis/ — Python, 45 lines3_comparison.py - src/
Colocalisation_analysis/ — Python, 158 lines4_colocalisation.py - src/
Proteomics_analysis/ — Python, 164 lines1_initial_cleanup.py - src/
Proteomics_analysis/ — Python, 105 lines2_normalisation.py - src/
Proteomics_analysis/ — Python, 93 lines3_ratio.py - src/
Proteomics_analysis/ — Python, 35 linesanalyse_go-enrichment.py - src/
Proteomics_analysis/ — Python, 40 linesanalyse_interactions.py - src/
Proteomics_analysis/ — Python, 82 linesheatmap.py - src/
Proteomics_analysis/ — Python, 167 linesplot_enrichment.py - src/
Proteomics_analysis/ — Python, 59 linesplot_ratios.py - src/
SR_analysis/ — Python, 56 lines1_initial_cleanup.py - src/
SR_analysis/ — Python, 358 lines2_localise.py - src/
SR_analysis/ — Python, 49 lines3_measure.py - src/
SR_analysis/ — Python, 100 lines, 1 matchSR_image_reconstruction. py - src/
SR_analysis/ — Python, 185 linesplot_comparison.py - LICENSE — License, 21 lines
- README.md — Text, 24 lines
The paper's code and data availability statement is in the Data section.
Tracing map
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Data
No dataset and no data link were found in the paper.
Data Availability Statement
All original code has been deposited at Zenodo at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, pages, dates, 9 authors, 5 keywords, 6 funders, 42 references.
Cite
This paper
Böken, D., Lobo, P. B., Wu, Y., Rowe, L. A., Fertan, E., Croft, C. L., Jimenez‐Sanchez, M., Cox, D., & Klenerman, D. (2026). Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e77822. https://
BibTeX
@article{boken2026tempor
author = {Böken, Dorothea and Lobo, Paula Beltran and Wu, Yunzhao and Rowe, Lyla A. and Fertan, Emre and Croft, Cara L. and Jimenez‐Sanchez, Maria and Cox, Dezerae and Klenerman, David},
title = {{Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = sep,
pages = {e77822},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {42750204},
pmcid = {PMC13583081}
}
RIS
TY - JOUR
AU - Böken, Dorothea
AU - Lobo, Paula Beltran
AU - Wu, Yunzhao
AU - Rowe, Lyla A.
AU - Fertan, Emre
AU - Croft, Cara L.
AU - Jimenez‐Sanchez, Maria
AU - Cox, Dezerae
AU - Klenerman, David
TI - Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
SP - e77822
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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"container-title": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
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"container-title-short":
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