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Tau extent is associated with lower cognition in Down syndrome-related Alzheimer's disease
Zammit MD, Hartley SL, Christian BT, Rafii MS.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026-10-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction 18 F-MK6240 is a second-generation tau positron emission tomography (PET) tracer with high dynamic range able to detect early tau pathology in Alzheimer's disease, however, its binding characteristics have not been evaluated in Down syndrome (DS), which is a population at high risk for early Alzheimer's disease onset. Past Down DS tau PET studies used 18 F-Flortaucipir, which suffers from off-target binding in early-stage regions, limiting pathology confirmation. This study evaluates the binding of 18 F-MK6240 in DS and examines the relationship between tau extent and cognition. Methods Tau Extent was measured in participants from the Trial Ready Cohort-Down Syndrome using 18 F-MK6240 and from the Alzheimer Alzheimer's Biomarker Consortium-Down Syndrome using 18 F-Flortaucipir. Data were compared, harmonized, and explored in relationship to cognitive endpoints with consideration of age, sex, apolipoprotein E (APOE) ε4 status, and level of intellectual disability. Results 18 F-MK6240 showed binding in the mesial temporal lobe shortly following the onset of beta-amyloid plaques, similar to our observations with 18 F-Flortaucipir. Increased tau extent correlated with lower episodic memory and overall cognitive performance scores. Age, intellectual disability level, and sex also influenced cognitive scores. Discussion This first evaluation of 18 F-MK6240 in DS demonstrates its suitability as a sensitive biomarker for Alzheimer's disease tau pathology. Furthermore, the inverse associations between Tau Extent as measured by both 18 F-MK6240 and 18 F-Flortaucipir and cognitive outcomes highlight the potential of these biomarkers to evaluate signs of early cognitive change, underscoring the urgent need to include this population in early clinical interventions.
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APA 7th
Zammit, M. D., Hartley, S. L., Christian, B. T., & Rafii, M. S. (2026). Tau extent is associated with lower cognition in Down syndrome-related Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71925
Vancouver
Zammit MD, Hartley SL, Christian BT, Rafii MS. Tau extent is associated with lower cognition in Down syndrome-related Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2026. doi:10.1002/alz.71925. PMID: 42928420.
BibTeX
@article{zammit2026-42928420,
author = {Zammit, M. D. and Hartley, S. L. and Christian, B. T. and Rafii, M. S.},
title = {{Tau extent is associated with lower cognition in Down syndrome-related Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
doi = {10.1002/alz.71925},
pmid = {42928420},
url = {https://doi.org/10.1002/alz.71925}
}
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Key findings
- Results 18 F-MK6240 showed binding in the mesial temporal lobe shortly following the onset of beta-amyloid plaques, similar to our observations with 18 F-Flortaucipir.
- Increased tau extent correlated with lower episodic memory and overall cognitive performance scores.
Study details
- Evidence strengthModerate
How this study scored 53/100
Published in a leading specialty 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 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 31 of the 58 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 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 | 2 / 2 | Indexed in PubMed (PMID 42928420) |
| Free to read | 2 / 2 | Free to read |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
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