P-tau 217 detects Alzheimer’s pathology in neurodegenerative syndromes
Key takeaways:
- P-tau 217 had high accuracy in diagnosing Alzheimer’s disease.
- P-tau 217 could also be a useful tool for detecting AD neuropathology in syndromes not commonly associated with AD.
Phosphorylated tau 217 better detected Alzheimer’s disease pathology across a range of neurodegenerative syndromes compared with other plasma blood-based biomarkers, data from a study in JAMA Neurology show.
“This article uses gold standard autopsy confirmation to show that a blood test for Alzheimer’s disease accurately detects the amyloid plaques and tau tangles across all clinical syndromes studied, even in syndromes not typically associated with Alzheimer’s disease,” Lawren VandeVrede, MD, PhD, assistant professor of neurology in the Memory and Aging Center and Weill Institute for Neurosciences at the University of California, San Francisco, told Healio.
Although blood-based biomarkers for detection of AD pathology are becoming more readily available, their clinical value is unclear when utilized for frontotemporal lobar degeneration syndromes (FTLD), VandeVrede and colleagues wrote.
They sought to examine both clinical importance and detectability of AD in FTLD-related neurodegenerative syndromes via three standard plasma biomarkers, phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).
Their retrospective study was conducted from August 2008 to July 2022 and included 349 deceased and autopsied individuals (55% men, mean age at death, 72 years) with records of both clinical evaluation and neuropathological examination. Among these, 125 were diagnosed with clinical syndromes related to AD, 198 with FTLD and 16 who were otherwise cognitively unimpaired at the time of evaluation.
While p-tau217 was measured with SIMOA single-molecule array, the other two were measured with commercially available SIMOA technology including Quanterix. AD was defined as intermediate or high AD neuropathological change (ADNC) at the time of an individual’s autopsy.
AD was confirmed in 167 of 349 individuals, including 45 of 198 who displayed evidence of FLTD-related syndromes.
Results showed plasma p-tau217 detected AD neuropathology (AUC = 0.95; 95% CI: 0.93-0.97), with slightly better performance in AD-related syndromes (AUC = 0.98; 95% CI: 0.95-1) compared with FTLD-related syndromes (AUC = 0.89; 95% CI, 0.83-0.94).
VandeVrede and colleagues also reported that NfL and GFAP recorded lower performance for AD detection (AUC = 0.73; 95% CI, 0.68-0.78; and AUC = 0.75; 95% CI, 0.67-0.8, respectively) while adding little to no diagnostic value by itself or in tandem with p-tau217.
The researchers also noted that plasma p-tau217 concentrations were higher in AD-related syndromes than FTLD-related syndromes, as well as highest in atypical AD-related syndromes, followed by typical late-onset amnestic syndromes.
Data additionally showed that AD was common in both AD- and FTLD-related syndromes while ADNC was higher in AD-related syndromes.
“Because this article shows that AD blood tests can be used in non-AD syndromes to detect clinically relevant neuropathology, this provides a new tool for trials to evaluate AD-targeting treatments in patients with clinical syndromes not typically associated with AD,” VandeVrede said.