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Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease
Kac PR, Alcolea D, Montoliu-Gaya L, Fernández S, Rodriguez JL, Maure L, González-Ortiz F, Benejam B et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-04-01
Topic: Brain proteins, microglia and lab models
Background All individuals with Down syndrome (DS) will develop full-blown Alzheimer´s disease (AD) pathology by age 40. Several genes encoded in chromosome 21, including dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), have been proven to contribute to the pathology. Phosphorylation of tau at threonine-212 (p-tau212) is very sensitive to DYRK1A phosphorylation and is increased in DSAD brain lysates. Here, we assessed the potential of this biomarker in DSAD and sporadic AD. Methods Using single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n = 245 for plasma, n = 114 matching cerebrospinal fluid [CSF] samples). Results We have confirmed that the levels of plasma p-tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states. Plasma p-tau212 started increasing approximately when people became amyloid positron emission tomography positive. Discussion Plasma p-tau212 might have utility for theragnostics, monitoring therapy efficacy, and as a target engagement biomarker in clinical trials both in sporadic and DSAD. Highlights Plasma p-tau212 is increased in the Down syndrome (DS) population. Plasma p-tau212 increases ≈15 years before the disease onset in DSAD. Plasma p-tau212 accurately differentiates between control and disease groups. Plasma p-tau212 accurately differentiates amyloid beta (Aβ)+ and Aβ- participants.
Key findings
- Results We have confirmed that the levels of plasma p-tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states.
Why it matters
Plasma p-tau212 was increased in people with Down syndrome and in sporadic Alzheimer's disease, including prodromal and mild cognitive impairment states, and began rising around when amyloid PET became positive. The authors suggest it might be useful for monitoring therapy efficacy and as a target engagement biomarker in trials, but no treatment was tested here.
Study details
- Participants245
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| 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 | 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 | 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 245 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 | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kaj Blennow: h-index 220 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40275833) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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APA 7th
Kac, P. R., Alcolea, D., Montoliu-Gaya, L., Fernández, S., Rodriguez, J. L., Maure, L., et al. (2025). Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70172
Vancouver
Kac PR, Alcolea D, Montoliu-Gaya L, Fernández S, Rodriguez JL, Maure L, et al. Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70172. PMID: 40275833.
BibTeX
@article{kac2025-40275833,
author = {Kac, P. R. and Alcolea, D. and Montoliu-Gaya, L. and Fernández, S. and Rodriguez, J. L. and Maure, L. and González-Ortiz, F. and Benejam, B. and others},
title = {{Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70172},
pmid = {40275833},
url = {https://doi.org/10.1002/alz.70172}
}
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