Plasma amyloid beta 40/42, phosphorylated tau 181, and neurofilament light are associated with cognitive impairment and neuropathological changes among World Trade Center responders: A prospective cohort study of exposures and cognitive aging at midlife.

Autor: Kritikos M; Program in Public Health and Department of Family Population, and Preventive Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Diminich ED; Program in Public Health and Department of Family Population, and Preventive Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Meliker J; Program in Public Health and Department of Family Population, and Preventive Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Mielke M; Department of Epidemiology and Prevention Wake Forest University School of Medicine Winston-Salem North Carolina USA., Bennett DA; Rush Alzheimer's Disease Center Rush University Chicago Illinois USA., Finch CE; Leonard Davis School of Gerontology University of Southern California Los Angeles California USA., Gandy SE; Department of Neurology Icahn School of Medicine at Mount Sinai New York New York USA.; Department of Psychiatry and Mount Sinai Alzheimer's Disease Research Center Icahn School of Medicine, Mount Sinai New York New York USA., Carr MA; Department of Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Yang X; Department of Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Kotov R; Department of Psychiatry Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Kuan PF; Department of Applied Mathematics Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Bromet EJ; Department of Psychiatry Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Clouston SAP; Program in Public Health and Department of Family Population, and Preventive Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA., Luft BJ; Department of Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (Amsterdam, Netherlands) [Alzheimers Dement (Amst)] 2023 Mar 08; Vol. 15 (1), pp. e12409. Date of Electronic Publication: 2023 Mar 08 (Print Publication: 2023).
DOI: 10.1002/dad2.12409
Abstrakt: Introduction: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology.
Methods: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample. We examined levels of the amyloid beta (Aβ)40/42 ratio, phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) and associations with a WTC exposures (duration on site ≥15 weeks, dust cloud), the PTSD Symptom Checklist for Diagnostic and Statistical Manual of Mental Disorders, 4th edition PTSD, and classification of amyloid/tau/neurodegeneration (AT[N]) profiles. Multinomial logistic regressions assessed whether biomarkers predicted increased risk of MCI or dementia.
Results: Of 1179 eligible responders, 93.0% were male, mean (standard deviation) age 56.6 years (7.8). Aβ40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data ( n = 75), Aβ40/42 and p-tau181 were further associated with decreased hippocampal volume (Spearman's  ρ = -0.3). Overall, 58.08% of responders with dementia had ≥1 elevated biomarker, and 3.45% had elevations across all biomarkers. In total, 248 (21.05%) had MCI and 70 (5.94%) had dementia. Increased risk of dementia was associated with plasma AT(N) profile T+ or A+N+. Exposure on site ≥15 weeks was independently associated with T+ (adjusted risk ratio [aRR] = 1.03 [1.01-1.05], P = 0.009), and T+N+ profile (aRR = 2.34 [1.12-4.87]). The presence of PTSD was independently associated with risk of A+ (aRR = 1.77 [1.11-2.82]).
Discussion: WTC exposures and chronic PTSD are associated with plasma biomarkers consistent with neurodegenerative disease.
Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information.
(© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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