By Lucy Piper, medwireNews Reporter
medwireNews: Plasma phosphorylated (p)-tau217 may be an effective biomarker for identifying patients with Alzheimer’s disease who are most likely to benefit from anti-amyloid immunotherapies based on amyloid (A)β positivity and tau pathology, say investigators.
Anti-amyloid immunotherapies are most effective in individuals who are Aβ positive and with minimal tau pathology, both normally assessed using positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers, the researchers explain in JAMA Neurology.
“Our findings have implications for streamlining patient management while minimizing the need for lumbar puncture and PET,” the team highlights.
Niklas Mattsson-Carlgren (Lund University, Sweden) and colleagues randomly assigned 912 people (mean age 71.1 years; 45.3% women) with subjective cognitive decline, mild cognitive impairment or dementia from the Swedish BioFINDER 2 study to a training (80%) or test (20%) set.
Among these individuals, 554 were confirmed as Aβ positive (CSF Aβ42/40 level <0.08) either by Aβ-PET or CSF, and 358 were found to be Aβ negative. Among the Aβ-positive patients, 52.9% had low tau PET, 26.2% had intermediate tau PET and 20.9% had high tau PET.
In the test set of patients, plasma p-tau217 was found to be the best of the biomarkers tested for ruling out Aβ-negative participants, others included p-tau181, p-tau231, N-terminal tau, glial fibrillary acidic protein and neurofilament light chain. When used as a stand-alone predictor, plasma p-tau217 was 92% accurate at ruling out Aβ-negative participants, based on a cutoff point of 0.22 ng/L.
When applied to the test group of patients, plasma p-tau217 identified patients who were Aβ positive with a sensitivity of 84% and a specificity of 88%.
The researchers then devised a two cutoff–point strategy for defining Aβ status, whereby plasma p-tau217 values were stratified into three categories, normal (<0.159 ng/L), indeterminate (0.159–0.219 ng/L) and abnormal (>0.219 ng/L), with the indeterminate group comprising a mix of Aβ-negative and positive patients.
At a sensitivity of 94% and a specificity of 86%, p-tau217 identified Aβ-positive patients in the test set with just 3.9% false negatives, 4.4% false positives; only 17.1% of patients in the indeterminate group would require CSF or PET to determine Aβ status.
The investigators note that not only was p-tau217 effective for distinguishing Aβ-positivity, it was also the best at identifying those individuals who had a high likelihood of having a high tau-PET uptake, with a 92% accuracy.
At a false-negative rate (FNR) of less than 10% (proportion of patients with high tau who were below the cutoff of 0.499 ng/L), the use of p-tau217 identified 56.9% of Aβ-positive patients with high tau uptake without the need for PET. It was also noninferior to CSF methods at identifying high tau PET among Aβ-positive patients, at an accuracy of 92% versus 85%.
“We believe that the 10% FNR is acceptable because there is still a weak effect of treatment in the high tau group,” say Mattsson-Carlgren and colleagues.
The findings were also similar when patients with subjective cognitive decline were excluded, and they were validated in an independent cohort of 118 patients.
Mattsson-Carlgren et al conclude: “Plasma p-tau217 measurement may be used as a first-in-line screening tool in management of patients with cognitive concerns, specifically for decision-making about treatment with antiamyloid immunotherapies in Alzheimer disease while limiting unnecessary invasive and costly biomarker testing.”
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JAMA Neurol 2023; doi:10.1001/jamaneurol.2023.4596