P-tau217 Distinguishes Alzheimer Disease From Other Neurodegenerative Diseases

Plasma tau phosphorylated at threonine 217 (P-tau217) can accurately differentiate Alzheimer disease (AD) from other neurodegenerative diseases compared with other established biomarkers, according to study results published in JAMA.

There has been improvement in AD diagnostics with the use of biomarkers to identify underlying disease pathologies. The goal of the current study was to investigate the diagnostic accuracy of plasma P-tau217 for AD, compared with other plasma, cerebrospinal fluid, and imaging biomarkers.

The multinational study included 3 cohorts. The first cohort consisted of 81 participants (34 with [immediate or high likelihood of] AD and 47 without AD) from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program. The second cohort consisted of 699 participants (121 with AD with dementia, 99 with other neurodegenerative diseases, 178 with mild cognitive impairment, and 301 cognitively unimpaired) from the Swedish BioFINDER-2 study (ClinicalTrials.gov Identifier: NCT03174938). Finally, the third cohort was comprised of 622 participants (365 PSEN1 E280A mutation carriers and 257 mutation non-carriers) from a Colombian autosomal-dominant AD registry.

The primary study outcome was the discriminative accuracy of plasma P-tau217 for the neuropathological or clinical diagnosis of AD.

In the Arizona cohort (mean age 83.5±8.5 years, 38% women), plasma P-tau217 discriminated neuropathologically defined AD from non-AD (area under the curve [AUC], 0.89; 95% CI, 0.81-0.97) and was significantly more accurate than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P <.05).

In the Swedish BioFINDER-2 cohort (mean age 69.1±10.3 years, 51% women), the discriminative accuracy of P-tau217 for clinical Alzheimer disease from other neurodegenerative conditions was 89% (AUC, 0.96; 95% CI, 0.93-0.98). This was significantly greater than for plasma P-tau181, plasma NfL, and magnetic resonance imaging (MRI) measures (AUC range, 0.50-0.81; P <.001). In addition, plasma P-tau217 levels accurately discriminated abnormal vs. normal tau-positron emission tomography (PET) status (AUC, 0.93; 95% CI, 0.91-0.96) significantly more than plasma P-tau181, plasma NfL, cerebrospinal fluid P-tau181, Aβ42:Aβ40 ratio, and MRI measures.

In the Colombian cohort (mean age 35.8±10.7 years, 57% women), levels of P-tau217 were significantly higher among carriers of PSEN1 mutation compared with non-carriers, starting around age 25 years and older; this was about 20 years before the mutation carriers’ estimated mild cognitive impairment onset.

Overall, findings indicated that plasma P-tau217 accurately discriminated clinically diagnosed AD from other neurodegenerative conditions, and differentiated patients with neuropathologically described AD from those lacking diagnostic levels of histopathology for AD. Plasma P-tau217 had significantly better diagnostic accuracy than plasma P-tau181, plasma NfL, and MRI measures. Its performance, however, did not significantly vary from those of key CSF- or PET-based measures. Furthermore, there was a correlation between plasma P-tau217 levels and cerebral tau tangles.

Study researchers acknowledged several study limitations, including the cross-sectional design, the inclusion of participants with P-tau217 levels below the detection limit, and the inclusion of 3 selected cohorts. Additionally, they noted the relatively small number of patients with other neurodegenerative diseases in cohort 2’s separate diagnostic groups.

“Although plasma P-tau217 was able to discriminate Alzheimer disease from other neurodegenerative diseases, further research is needed to validate the findings in unselected and diverse populations, optimize the assay, and determine its potential role in clinical care,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020;324(8):772-781. doi:10.1001/jama.2020.12134