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Differing network patterns of functional connectivity and amyloid PET between tau PET subtypes
Peter R Millar, Stephanie Doering, Babatunde Adeyemo, Nicole Sarah McKay, Nicholas V. Metcalf, June Roman, Pete Canfield, Saurabh Jindal et al.. Alzheimer s & Dementia, 2025-12-01
Topic: Brain proteins, microglia and lab models
Abstract Background Spatiotemporal patterns of tau accumulation differ between distinct Alzheimer disease (AD) phenotypes and can be identified with PET imaging. Tau accumulation may be driven in part by trans‐neuronal spreading through network connections, which can be estimated using resting state functional connectivity MRI (RSFC), and by amyloid‐β (Aβ) deposition. We aimed to replicate tau PET subtypes and tested subtype‐specific differences in network patterns of RSFC and Aβ PET. Method We used the Subtype and Stage Inference (SuStaIn) model to identify spatiotemporal patterns in 820 tau PET scans ( 18 F‐flortaucipir) from 629 Knight ADRC participants (mean age = 70.3, SD = 8.6, N = 690 CDR® 0, N = 130 CDR > 0). RSFC correlations were analyzed using seeds in primary visual cortex (V1) and precuneus/posterior cingulate cortex (PCC). Aβ PET SUVRs using 11 C‐Pittsburgh‐compound‐B (PiB, N = 365) or 18 F‐florbetapir (FBP, N = 423) were harmonized to Centiloid. Result We identified three tau PET subtypes, resembling previously reported patterns: limbic predominant ( N = 157), posterior predominant ( N = 27), and medial temporal lobe (MTL)‐sparing ( N = 52), Figure 1. The remaining scans were tau‐negative ( N = 570) or had unstable classifications ( N = 14). MTL‐sparing participants were younger, more severely impaired, and had greater levels of Aβ PET than other groups ( p ’s < 0.001). Posterior predominant participants were less frequently APOE ε4 carriers than limbic predominant participants ( p ’s < 0.001). Although posterior predominant participants exhibited lower levels of Aβ PET than limbic predominant participants in anterior regions and global summaries, Aβ PET was slightly greater in occipital regions, Figure 2. Compared to limbic predominant participants, posterior predominant participants exhibited stronger RSFC correlations between V1 and adjacent regions within the visual network and other networks, Figure 3. MTL‐sparing participants exhibited stronger RSFC correlations between PCC and other default mode regions throughout the cortex. Conclusion We replicated three distinct spatiotemporal subtypes of tau PET accumulation and their associations with individual differences and AD severity in an independent sporadic AD cohort. We identified novel differences in spatial patterns of Aβ PET and RSFC, which may contribute to or result from unique patterns of tau spreading within these subtypes.
Key findings
- Result We identified three tau PET subtypes, resembling previously reported patterns: limbic predominant ( N = 157), posterior predominant ( N = 27), and medial temporal lobe (MTL)‐sparing ( N = 52), Figure 1.
- Compared to limbic predominant participants, posterior predominant participants exhibited stronger RSFC correlations between V1 and adjacent regions within the visual network and other networks, Figure 3.
- We identified novel differences in spatial patterns of Aβ PET and RSFC, which may contribute to or result from unique patterns of tau spreading within these subtypes.
Why it matters
Three tau PET subtypes were identified, and the MTL-sparing group was younger, more impaired, and had greater amyloid PET levels than other groups. The findings describe differences in network patterns and amyloid across tau subtypes, which may help explain varied disease presentations.
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Study details
- Participants690
- Evidence strengthModerate
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 690 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Tammie L.S. Benzinger: h-index 98 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41434143) |
| Free to read | 2 / 2 | Free to read |
| Total | 40 / 100 | — |
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Read the original
- DOI: 10.1002/alz70862_109964
- PubMed: 41434143
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Millar, P. R., Doering, S., Adeyemo, B., McKay, N. S., Metcalf, N. V., Roman, J., et al. (2025). Differing network patterns of functional connectivity and amyloid PET between tau PET subtypes. Alzheimer s & Dementia. https://doi.org/10.1002/alz70862_109964
Vancouver
Millar PR, Doering S, Adeyemo B, McKay NS, Metcalf NV, Roman J, et al. Differing network patterns of functional connectivity and amyloid PET between tau PET subtypes. Alzheimer s & Dementia. 2025. doi:10.1002/alz70862_109964. PMID: 41434143.
BibTeX
@article{millar2025-41434143,
author = {Millar, Peter R and Doering, Stephanie and Adeyemo, Babatunde and McKay, Nicole Sarah and Metcalf, Nicholas V. and Roman, June and Canfield, Pete and Jindal, Saurabh and others},
title = {{Differing network patterns of functional connectivity and amyloid PET between tau PET subtypes}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70862_109964},
pmid = {41434143},
url = {https://doi.org/10.1002/alz70862_109964}
}