Fine Particulate Matter Exposure and Cerebrospinal Fluid Markers of Vascular Injury

Article type: Research Article

Authors: Shaffer, Rachel M.^a | Sheppard, Lianne^{a; b} | Peskind, Elaine R.^{c; d} | Zhang, Jing^e | Adar, Sara D.^f | Li, Ge^{c; d; g; *}

Affiliations: [a] Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA | [b] Department of Biostatistics, University of Washington, Seattle, WA, USA | [c] VA Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA | [d] Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA | [e] Department of Pathology, University of Washington, Seattle, WA, USA | [f] Department of Environmental Health Sciences, University of Michigan, Ann Arbor, WA, USA | [g] Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA

Correspondence: [*] Correspondence to: Ge Li, S182 GRECC, VAPSHCS, 1660 S. Columbian Way, Seattle, WA 98108, USA. Tel.: +1 206 764 2485; E-mail: [email protected].

Abstract: Background: Cerebrovascular diseases play an important role in dementia. Air pollution is associated with cardiovascular disease, with growing links to neurodegeneration. Prior studies demonstrate associations between fine particulate matter (PM2.5) and biomarkers of endothelial injury in the blood; however, no studies have evaluated these biomarkers in cerebrospinal fluid (CSF). Objective: We evaluate associations between short-term and long-term PM2.5 exposure with CSF vascular cell adhesion molecule-1 (VCAM-1) and e-selectin in cognitively normal and mild cognitive impairment (MCI)/Alzheimer’s disease (AD) individuals. Methods: We collected CSF from 133 community volunteers at VA Puget Sound between 2001–2012. We assigned short-term PM2.5 from central monitors and long-term PM2.5 based on annual average exposure predictions linked to participant addresses. We performed analyses stratified by cognitive status and adjusted for key covariates with tiered models. Our primary exposure windows for the short-term and long-term analyses were 7-day and 1-year averages, respectively. Results: Among cognitively normal individuals, a 5 μg/m3 increase in 7-day and 1-year average PM2.5 was associated with elevated VCAM-1 (7-day: 35.4 (9.7, 61.1) ng/ml; 1-year: 51.8 (6.5, 97.1) ng/ml). A 5 μg/m3 increase in 1-year average PM2.5, but not 7-day average, was associated with elevated e-selectin (53.3 (11.0, 95.5) pg/ml). We found no consistent associations among MCI/AD individuals. Conclusions: We report associations between short-term and long term PM2.5 and CSF biomarkers of vascular damage in cognitively normal adults. These results are aligned with prior research linking PM2.5 to vascular damage in other biofluids as well as emerging evidence of the role of PM2.5 in neurodegeneration.

Keywords: Alzheimer’s disease, biomarkers, cellular adhesion molecules, cerebrospinal fluid, cerebrovascular disorders, dementia, particulate matter

DOI: 10.3233/JAD-190563

Journal: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 1015-1025, 2019