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Mesoscale medial temporal lobe connectivity patterns relate to tau pathology and memory in older adults
Fischer L, Vockert N, Höpker Fernandes J, Garcia-Garcia B, Roemer-Cassiano SN, Franzmeier N, Gellersen HM, Schumann-Werner B et al.. bioRxiv, 2026-08-21
Topic: Plasma and spinal-fluid biomarkers
The medial temporal lobe (MTL) is crucial for episodic memory. Tau pathology is a hallmark of Alzheimer’s disease (AD) and accumulates in layer-specific patterns in the MTL during aging. It is, however, unclear whether early AD pathology relates to mesoscale network signatures distinct from non-pathological aging. To address this gap, we acquired 7 Tesla submillimeter-resolution resting-state fMRI, plasma-based AD biomarkers, glial fibrillary acidic protein (GFAP) levels, APOE genotype, regional [ 18 F]PI-2620 tau PET burden, and longitudinal episodic memory data in 75 cognitively unimpaired older adults. Older age was associated with lower perirhinal– hippocampal connectivity and lower network segregation, whereas higher plasma-based AD pathology was associated with higher perirhinal–hippocampal connectivity. Furthermore, temporal-lobe tau burden was related to altered connectivity patterns in tau-vulnerable MTL subfields and layers, dependent on GFAP levels. Retrosplenial tau burden was associated with higher hippocampal-retrosplenial connectivity consistent with tau spread along canonical hippocampal output pathways. Finally, higher connectivity within the hippocampus attenuated the negative association between temporal-lobe tau burden and memory performance but predicted unfavorable memory trajectories. Our findings show differential associations of age and AD pathology with mesoscale MTL-connectivity patterns. Importantly, increased hippocampal connectivity may support memory function in the short term while contributing to subsequent memory decline.
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APA 7th
Fischer, L., Vockert, N., Höpker Fernandes, J., Garcia-Garcia, B., Roemer-Cassiano, S. N., Franzmeier, N., et al. (2026). Mesoscale medial temporal lobe connectivity patterns relate to tau pathology and memory in older adults. bioRxiv. https://doi.org/10.64898/2026.08.18.745399
Vancouver
Fischer L, Vockert N, Höpker Fernandes J, Garcia-Garcia B, Roemer-Cassiano SN, Franzmeier N, et al. Mesoscale medial temporal lobe connectivity patterns relate to tau pathology and memory in older adults. bioRxiv. 2026. doi:10.64898/2026.08.18.745399.
BibTeX
@article{fischer2026-209ac9cc,
author = {Fischer, L. and Vockert, N. and Höpker Fernandes, J. and Garcia-Garcia, B. and Roemer-Cassiano, S. N. and Franzmeier, N. and Gellersen, H. M. and Schumann-Werner, B. and others},
title = {{Mesoscale medial temporal lobe connectivity patterns relate to tau pathology and memory in older adults}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.08.18.745399},
url = {https://doi.org/10.64898/2026.08.18.745399}
}
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Key findings
- Older age was associated with lower perirhinal– hippocampal connectivity and lower network segregation, whereas higher plasma-based AD pathology was associated with higher perirhinal–hippocampal connectivity.
- Retrosplenial tau burden was associated with higher hippocampal-retrosplenial connectivity consistent with tau spread along canonical hippocampal output pathways.
- Our findings show differential associations of age and AD pathology with mesoscale MTL-connectivity patterns.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 22 of the 62 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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