Abstract
Alzheimers Dement. 2025 Apr;21(4):e70172. doi: 10.1002/alz.70172.
ABSTRACT
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.
PMID:40275833 | DOI:10.1002/alz.70172
UK DRI Authors
