Home › Research › Inflammation and the immune system
Neuropathological perspectives on neuroinflammation and tau molecular imaging in frontotemporal lobar degeneration
Rodolfo G. Gatto, Hossam Youssef, Mu‐Hui Fu, R. Ross Reichard, Val J. Lowe, Jennifer L. Whitwell, Keith A. Josephs, Gokhan Uruk. Discover Neuroscience, 2026-06-28
Topic: Brain proteins, microglia and lab models
Flortaucipir (FTP) PET imaging was developed to quantify tau burden in tauopathies such as Alzheimer’s disease (AD) and to distinguish AD from other dementias, including frontotemporal lobar degeneration (FTLD). In FTLD-tau, FTP uptake in subcortical regions is often considered off-target binding. However, tau aggregation has been associated with neuroinflammation and oxidative stress. This study investigates whether FTP uptake in FTLD-tau overlaps with neuroinflammatory and iron-related oxidative markers. We analyzed postmortem brain samples from eight individuals: two controls, one intermediate-likelihood AD (I-AD), one high-likelihood AD (H-AD), and four FTLD-tau subtypes; progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), globular glial tauopathy (GGT), and Pick’s disease (PiD). We performed fluorescence FTP analog (T726) and staining targeting neuroinflammatory markers (GFAP, IBA1, CD68), and iron via ferritin light-chain (Ferr). Samples were taken from the superior/middle frontal gyri (S/M-FG) and basal ganglia (BG), including the putamen (Pu), globus pallidus externus (GPe), and internus (GPi). FTP binding was assessed using a fluorescent analog (T726) and confocal imaging, with comparisons to premortem PET scans. We observed increased activation of GFAP+ astrocytes and microglia/macrophages in both cortical and subcortical regions, with tau deposition detected in AD and FTLD-tau cases. Distinct neuroinflammatory patterns emerged across FTLD-tau subtypes, notably in PSP and CBD. Colocalization of GFAP+, IBA1, CD68, Ferr, and T726 signals suggest that FTP uptake in FTLD-tau may reflect gliosis and neuroinflammation. These findings indicate that neuroinflammation, gliosis, and possibly oxidative stress may contribute to elevated FTP signals in FTLD-tau, offering insight into the biological underpinnings of tracer uptake beyond tau pathology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gatto, R. G., Youssef, H., Fu, M., Reichard, R. R., Lowe, V. J., Whitwell, J. L., et al. (2026). Neuropathological perspectives on neuroinflammation and tau molecular imaging in frontotemporal lobar degeneration. Discover Neuroscience. https://doi.org/10.1186/s13064-026-00292-3
Vancouver
Gatto RG, Youssef H, Fu M, Reichard RR, Lowe VJ, Whitwell JL, et al. Neuropathological perspectives on neuroinflammation and tau molecular imaging in frontotemporal lobar degeneration. Discover Neuroscience. 2026. doi:10.1186/s13064-026-00292-3.
BibTeX
@article{gatto2026-b272180f,
author = {Gatto, Rodolfo G. and Youssef, Hossam and Fu, Mu‐Hui and Reichard, R. Ross and Lowe, Val J. and Whitwell, Jennifer L. and Josephs, Keith A. and Uruk, Gokhan},
title = {{Neuropathological perspectives on neuroinflammation and tau molecular imaging in frontotemporal lobar degeneration}},
journal = {Discover Neuroscience},
year = {2026},
doi = {10.1186/s13064-026-00292-3},
url = {https://doi.org/10.1186/s13064-026-00292-3}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- However, tau aggregation has been associated with neuroinflammation and oxidative stress.
- We observed increased activation of GFAP+ astrocytes and microglia/macrophages in both cortical and subcortical regions, with tau deposition detected in AD and FTLD-tau cases.
- Colocalization of GFAP+, IBA1, CD68, Ferr, and T726 signals suggest that FTP uptake in FTLD-tau may reflect gliosis and neuroinflammation.
- These findings indicate that neuroinflammation, gliosis, and possibly oxidative stress may contribute to elevated FTP signals in FTLD-tau, offering insight into the biological underpinnings of tracer uptake beyond tau pathology.
Why it matters
In postmortem samples from eight individuals, tau PET tracer binding in frontotemporal lobar degeneration overlapped with markers of gliosis and neuroinflammation. This is a small tissue study about what imaging signals reflect, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 33 of the 96 points we could judge it on, which is 34 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Discover Neuroscience) |
| Journal's citation record | 0 / 4 | Discover Neuroscience: journal h-index 6 (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 | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.2× 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 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Gokhan Uruk holds only 8 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 33 of the 96 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Inflammation and the immune system
Also tagged “phosphorylated”
732 studies in the library carry the topic tag “phosphorylated”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 732 tagged studies.