23 feb. 2025
A recent study published in JAMA Neurology explored the clinical potential of blood-based biomarkers such as pTau217, GFAP, and NfL to detect Alzheimer’s disease (AD) even in syndromes typically linked to frontotemporal lobar degeneration (FTLD). Here’s what they found:
Key Findings:
High Prevalence of AD: AD was present in 88% of AD-related syndromes and 23% of FTLD-related syndromes, highlighting its widespread impact. The intermediate and high ADNC criteria were used to determine the AD neuropathology.
Biomarker Accuracy: Plasma p-tau217 demonstrated an impressive diagnostic accuracy (AUC = 0.95) for identifying Alzheimer’s disease neuropathology across different clinical syndromes, whereas neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) added little value.
Clinical Relevance: AD in FTLD-related syndromes was linked to worse cognitive performance and increased posterior cortical atrophy, emphasizing the importance of identifying AD copathology.
Challenges:
Relying solely on Alzheimer's disease biomarkers may lead to misdiagnosis, especially when the selection of these biomarkers is influenced by existing or developing neuropathology at the time of assessment.
Complex Copathology: Alzheimer's disease as a copathology can present in many neurodegenerative scenarios, complicating diagnosis and treatment strategies, and requiring a nuanced interpretation of biomarker results.
My Take:
This study underscores the importance of integrating blood biomarkers into diagnostic workflows, not just for typical Alzheimer’s but also for non-AD neurodegenerative syndromes. In the study, plasma p-tau217 effectively detected intermediate to high ADNC stages, demonstrating high diagnostic accuracy. This makes it a promising blood-based biomarker for identifying AD even in atypical or non-AD clinical syndromes, especially as disease-modifying treatments for AD advance.