VandeVrede L, Cho H, Sanderson-Cimino M, Wekselman F, Cobigo Y, Gorno-Tempini ML, Heuer HW, Kramer JH, Lario Lago A, Leichter D, Ljubenkov P, Miller BL, Perry DC, Rabinovici GD, Rojas JC, Rosen HJ, Saloner R, Staffaroni A, Triana-Baltzer G, Spina S, Seeley WW, Grinberg LT, Kolb HC, La Joie R, Boxer AL. Detection of Alzheimer Neuropathology in Alzheimer and Non-Alzheimer Clinical Syndromes With Blood-Based Biomarkers. JAMA Neurol. 2025 Feb 10; Epub 2025 Feb 10 PubMed.
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Washington University
This very important and well-performed study by Drs. Vandevrede, Boxer, and colleagues includes both neuropathology and blood biomarkers on patients with well-characterized clinical syndromes. They found that Alzheimer's disease co-pathology was common across clinical syndromes including in dementia with Lewy bodies and frontotemporal lobar degeneration syndromes. Importantly, plasma p-Tau217 consistently distinguished between individuals with and without Alzheimer disease pathology, regardless of the clinical syndrome, although it performed slightly better in those with Alzheimer's disease syndromes. Plasma NfL was higher in non-AD syndromes, while GFAP was higher in AD syndromes.…More
Overall, this study reinforces the concepts that clinical syndromes may have multiple underlying causes/associated neuropathologies, and the role of biomarkers is to help identify the likely primary neuropathology. The authors emphasize that relying only on biomarkers (e.g., plasma p-Tau217) may lead to misdiagnosis given the high prevalence of AD co-pathology, and that it is essential to integrate biomarkers with clinical findings to reach an accurate diagnosis.
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