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

Details

• Personal Author:
  Bromet EJ ; Carr M ; Clouston SAP ; Deri Y ; Diminich ED ; Gandy S ; Kritikos M ; Luft BJ ; Sano M ; Yang X
• Description:
  Introduction: 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 B-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 AB40 subtype in A is not well understood. This study examined plasma-based neuropathological markers of AB42 and AB40 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 B-amyloid subtypes in the ATN model. Methods: 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. Results: Our findings support the ATN neuropathological cascade model of AD and further identify an associative role for AB40 in A as playing a central role linking T to N. A strong correlation was found between CI and age, and it was found that women may be at increased risk of elevated T levels, with plasma NfL levels higher in responders with CI. Notably, our model reported associations between: AB42, CI and N; AB40, T and N; T and CI; AB42 and AB40. Conclusions: The current ATN model of AD does not specify the subtype of B-amyloid to be considered, which may be overlooking the differential roles that these two subtypes serve in the pathogenesis of AD. [Description provided by NIOSH]
• Subjects:
  Biomarkers Emergency Responders Nervous System Nervous System Diseases Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  β-amyloid Alzheimers Disease Author Keywords: ATN Cognitive Function Cognitive Impairment Dementia Disaster Recovery Emergency Responders First Responders Neurofilament Light Neurological Disorders Neuropathology Pathway Analysis Plasma Rescue Workers Tau World Trade Center WTC

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• ISSN:
  2193-8253
• Document Type:
  Text
• Funding:
  Contract
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  159-171
• Volume:
  9
• Issue:
  1
• NIOSHTIC Number:
  nn:20059476
• Citation:
  Neurol Ther 2020 Jun; 9(1):159-171
• Contact Point Address:
  Minos Kritikos, Department of Family, Population and Preventive Medicine, Program in Public Health, Renaissance School of Medicine at Stony Brook, Stony Brook, NY
• Email:
  minos.kritikos@stonybrookmedicine.edu
• Federal Fiscal Year:
  2020
• Peer Reviewed:
  True
• Source Full Name:
  Neurology and Therapy
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:91f7c8bf3064fc96d70d78abf28738b0302467dc2210a94f088e929b75c3bba0d9a378d6e794bd283f177d3e419311affe90b454d7c817ced0d8d095f31c55bb
• Download URL:
  https://stacks.cdc.gov/view/cdc/223694/cdc_223694_DS1.pdf
• File Type:
  [PDF - 696.55 KB ]