Highly Accurate Biomarker for Alzheimer Disease Identified

 

New data presented at the Alzheimer’s Association International Conference indicates that measuring p-tau217 levels in plasma and cerebrospinal fluid (CSF) can detect Alzheimer disease (AD) with high accuracy.

“Plasma and CSF p-tau217 reflect brain tau burden, increases early in AD, and differentiates AD from other neurodegenerative diseases,” the authors of the study wrote.1

The findings could have important future implications, according to lead author Oskar Hansson, PhD. “This test, once verified and confirmed, opens the possibility of early diagnosis of Alzheimer’s before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” said Dr Hansson in a press release.2

Dr Hansson and colleagues arrived at their conclusion after comparing CSF p-tau217 with CSF p-tau181, an established biomarker for AD, in the following cohorts:

  • The SwedishBioFINDER-1 cohort, which included 194 participants
  • The SwedishBioFINDER-2 cohort, which included 312 participants without cognitive impairment, 188 patients with clinically diagnosed mild cognitive impairment, 126 patients with AD dementia, and 109 participants with other non-AD neurodegenerative diseases
  • A neuropathology cohort in Arizona, which included 34 participants with AD and 47 participants without AD
  • A Colombian autosomal-dominant AD kindred, which included 365 PSEN1​E280A-carriers and 257 non-mutation carriers


The results of the study indicated that CSF p-tau217 was more strongly correlated with the tau- positron emission tomography (PET) tracer and was more accurate in identifying participants with abnormal tau-PET scans compared with CSF p-tau181. In addition, CSF p-tau217 was found to correlate better with CSF and PET measures of neocortical amyloid-β burden and distinguished AD dementia from non-AD neurodegenerative disorders more accurately than p-tau181.

Antemortem plasma p-tau217 performed significantly better than plasma p-tau181 and was able to differentiate individuals whose risk of AD was intermediate to high, as determined by neuropathology, from individuals without AD. In differentiating clinical AD dementia from non-AD neurodegenerative diseases, plasma p-tau217 performed significantly better than plasma p-tau181, plasma neurofilament light, and established magnetic resonance imaging (MRI) measures; and performed similarly to CSF p-tau217, CSF p-tau181, CSF Aβ42/40, and tau-PET.

The researchers noted that increased plasma p-tau217 occurred in pre-symptomatic stages of AD, and that plasma p-tau217 correlated with cerebral tau tangle densities among patients with neuritic plaques. Furthermore, they found that plasma p-tau217 was a significantly better predictor of abnormal tau-PET scans than plasma p-tau181, CSF p-tau181, plasma neurofilament light, and CSF Aβ42/Aβ40. Plasma and CSF p-tau217 predicted abnormal tau-PET scans similarly.

—Christina Vogt

References:

  1. Hansson O. Phospho-tau217 and phospho-tau181 in plasma and CSF as biomarkers for Alzheimer’s disease. Paper presented at: Alzheimer’s Association International Conference; July 27-31, 2020; Virtual. https://www.alz.org/aaic/downloads2020/AAIC2020-BloodBiomarkers.pdf
  2. A blood test for Alzheimer’s disease? Markers for tau take us a step closer. News release. Alzheimer’s Association. July 28, 2020. Accessed July 28, 2020. https://www.alz.org/aaic/downloads2020/AAIC2020-BloodBiomarkers.pdf