P4‐530: PHOSPHORYLATED TAU INTERACTOME IN THE HUMAN ALZHEIMER'S DISEASE BRAIN
Bibliographic record
Abstract
Accumulation of phosphorylated tau (pTau) is a key pathological feature of Alzheimer's disease. pTau accumulation causes synaptic impairment, neuronal dysfunction and formation of neurofibrillary tangles. The pathological actions of pTau are likely mediated by surrounding neuronal proteins, however our knowledge of the specific proteins that pTau interacts with in Alzheimer's disease is surprisingly limited. Therefore, the aim of this study was to comprehensively map the pTau interactome for the first time. We used two complementary proteomics approaches to map the pTau interactome. First, quantitative proteomics was performed on neurofibrillary tangles microdissected from patients with advanced Alzheimer's disease (n=7 cases). Second, affinity purification-mass spectrometry was used to identify which of these proteins specifically bound to PHF1-immunoreactive pTau in the Alzheimer's disease brain (n=5 cases). 542 proteins were identified in neurofibrillary tangles. The abundant detection of proteins known to be present in neurofibrillary tangles including tau, ubiquitin, neurofilament proteins, ApoE and CDK5 validated our approach. Affinity purification-mass spectrometry confirmed that 75 of these 542 proteins were pTau binding partners. 34 proteins had been identified in previous studies to interact with pTau. More excitingly, an additional 34 proteins had previously been associated with Alzheimer's disease, but not linked directly to tau (e.g. synaptic protein VAMP2, RNA binding protein HNRNPA1), therefore we provide new evidence that their role in Alzheimer's disease likely involves their interaction with pTau. In addition, we also identified 7 novel proteins, not previously known to be associated with Alzheimer's disease or with tau. Network analysis showed that the pTau interactome was enriched in proteins involved in phagosome maturation and the protein ubiquitination pathway. Importantly, we were able to pinpoint the specific proteins that pTau interacts with in these pathways for the first time, therefore providing novel pathogenic mechanisms that can be explored in future studies. We present the first comprehensive analysis of the pTau interactome in the human Alzheimer's disease brain. These results reveal novel potential drug targets for the treatment of tauopathies and provide insight into how pTau mediates its pathological effects in Alzheimer's disease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".