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

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 Ultrasensitive Simoa technology was utilized to measure neuropathology in plasma collected from a consecutive clinical sample (n =398). Generalized structural equation modeling was utilized for modeling linkages between pathological markers. Model fit was utilized to determine proposed directions of association. Our findings support the ATN neuropathological cascade model of AD and further identify an associative role for Aβ The current ATN model of AD does not specify the subtype of β-amyloid to be considered, which may be overlooking the differential roles that these two subtypes serve in the pathogenesis of AD.