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Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease
Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Huang Y, Yang Y et al.. Molecular psychiatry, 2024-04-08
Topic: Brain proteins, microglia and lab models
The associations of synaptic loss with amyloid-β (Aβ) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [ 18 F]SynVesT-1 PET/MR scans to assess synaptic density and [ 18 F]florbetapir and [ 18 F]MK6240 PET/CT scans to evaluate Aβ plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aβ42/40 and p-tau181 levels measured by the Simoa platform. Twenty-three individuals, 6 AD patients, 4 MCI patients, and 13 NCs, underwent [ 18 F]SynVesT-1 PET/MRI and [ 18 F]MK6240 PET/CT scans during a one-year follow-up assessment. The associations of Aβ and tau pathology with cross-sectional and longitudinal synaptic loss were investigated using Pearson correlation analyses, generalized linear models and mediation analyses. AD patients exhibited lower synaptic density than NCs and MCI patients. In the whole cohort, global Aβ deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes. Synaptic density in almost all regions was related to the corresponding regional tau tangles independent of global Aβ deposition in the whole cohort and stratified groups. Synaptic density in the medial and lateral temporal lobes was correlated with plasma Aβ42/40 (r = 0.300, p = 0.020/r = 0.289, p = 0.025) and plasma p-tau 181 (r = -0.412, p = 0.001/r = -0.529, p < 0.001) levels in the whole cohort. Mediation analyses revealed that tau tangles mediated the relationship between Aβ plaques and synaptic density in the whole cohort. Baseline tau pathology was positively associated with longitudinal synaptic loss. This study suggested that tau burden is strongly linked to synaptic density independent of Aβ plaques, and also can predict longitudinal synaptic loss.
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APA 7th
Wang, J., Huang, Q., Chen, X., You, Z., He, K., Guo, Q., et al. (2024). Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/s41380-024-02501-z
Vancouver
Wang J, Huang Q, Chen X, You Z, He K, Guo Q, et al. Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease. Molecular psychiatry. 2024. doi:10.1038/s41380-024-02501-z. PMID: 38589563.
BibTeX
@article{wang2024-38589563,
author = {Wang, J. and Huang, Q. and Chen, X. and You, Z. and He, K. and Guo, Q. and Huang, Y. and Yang, Y. and others},
title = {{Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2024},
doi = {10.1038/s41380-024-02501-z},
pmid = {38589563},
url = {https://doi.org/10.1038/s41380-024-02501-z}
}
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Key findings
- In the whole cohort, global Aβ deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes.
- Mediation analyses revealed that tau tangles mediated the relationship between Aβ plaques and synaptic density in the whole cohort.
- Baseline tau pathology was positively associated with longitudinal synaptic loss.
- This study suggested that tau burden is strongly linked to synaptic density independent of Aβ plaques, and also can predict longitudinal synaptic loss.
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Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 55/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38589563) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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