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World Trade Center (WTC) responders who aided in the search and rescue efforts are now at midlife, and evidence has demonstrated that many are experiencing early-onset cognitive impairment and are at risk of developing dementia, such as Alzheimer's disease (AD). According to the recent NIA-AA framework, AD is characterized by a neuropathological cascade commencing with β-amyloid deposition (A), followed by tauopathy (T) and neurodegeneration (N). However, the ATN model has not been replicated utilizing recently validated plasma-based biomarkers, and the role of the Aβ 40 subtype in A is not well understood. This study examined plasma-based neuropathological markers of Aβ 42 and Aβ 40 for A, total tau for T, and NfL for N in a cohort of World Trade Center responders at midlife in order to determine the role for the two β-amyloid subtypes in the ATN model.

Pathway Analysis for Plasma β-Amyloid, Tau and Neurofilament Light (ATN) in World Trade Center Responders at Midlife