Plasma assays ‘accurately rule out’ AD-related pathology

Key takeaways:

• The negative predictive value of the combined pTau181 and ApoE4 assays was 96.2%
• The rule-out performance of pTau 181 alone was 97.6%.

Plasma pTau181 in combination with ApoE4 assays registered a high degree of accuracy in ruling out patients with a low probability of amyloid pathology in the early stages of Alzheimer’s disease, according to a poster presentation at CTAD.

“Alzheimer's is often underdiagnosed with no known cure,” Margherita Carboni, PhD, neurology indication lead at Roche Diagnostics, which funded the study, told Healio in an email. “There are options to manage symptoms and even some recently approved disease-modifying treatments, but these work best when given early on, so timelier diagnosis is paramount.”

Early detection of amyloid pathology is critical to formulate a treatment plan in those who may develop AD, with blood-based biomarkers positioned as emergent rapid diagnostic tools, the researchers wrote.

They analyzed the efficacy of different blood-based biomarker immunoassays for ruling out amyloid pathology indicative of AD in a cohort of older adults.

Their prospective multicenter study included 492 individuals (mean age, 69.2 years; 62.4% women) who were recruited from 12 clinical sites across the U.S. and Europe with a diagnosis of either subjective cognitive decline (SCD), mild cognitive impairment (MCI) or mild dementia and were evaluated for AD or other causes of cognitive decline.

The researchers used Elecsys pTau181 and ApoE4 plasma assays from Roche to analyze plasma samples. The discriminative ability of both pTau181 and ApoE4 regarding amyloid PET status via MRI and to cerebrospinal fluid ratio of the Elecsys Phospho-Tau (181P) and Elecsys Amyloid (1-42) II CSF assays were measured in relation to both negative and positive predictive values.

The clinical performance of pTau181 combined with ApoE4, as well as pTau181 alone, were assessed.

In all, 475 enrollees had amyloid PET results (23.4% positive), 360 participants had CSF results (31.9% positive) and 343 individuals had PET/CSF crossovers.

Based on an amyloid positivity prevalence of 23.4% (via amyloid PET), the results showed the negative predictive value (NPV) of the combined assays was 96.2%, paired with a positive predictive value of 47.9%, with a sensitivity of 91% and specificity of 69.8%.

The rule-out performance of pTau181 alone was similar (NPV = 97.6%; PPV = 46.1%), although, analyzed with ApoE4, the clinical performance leaned towards analytical variability.

“The results show that the p-Tau181 test can accurately rule out amyloid pathology with high certainty through a simple blood test,” Carboni told Healio. “This offers reassurance, avoids the need for unnecessary burdensome testing, and guides treatment decisions.”