Plasma p‐tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease

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.