The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people
Por:
Jacobs, T, Jacobson, SR, Fortea, J, Berger, JS, Vedvyas, A, Marsh, K, He, TS, Gutierrez-Jimenez, E, Fillmore, NR, Gonzalez, M, Figueredo, L, Gaggi, NL, Plaska, CR, Pomara, N, Blessing, E, Betensky, R, Rusinek, H, Zetterberg, H, Blennow, K, Glodzik, L, Wisniweski, TM, de Leon, MJ, Osorio, RS, Ramos-Cejudo, J
Publicada:
17 may 2024
Resumen:
Background An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-beta 42 (A beta 42), total tau (t-tau), and phosphorylated tau(181) (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. Results A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of A beta-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF A beta 42 (beta = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (beta = 26.812, p = 0.019) and p-tau (beta = 3.441, p = 0.015), but not A beta 42. In the NYU cohort alone, subjects classified as A beta + (n = 38) displayed a stronger association between the NLR and t-tau (beta = 100.476, p = 0.037) compared to A beta- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions We report associations between the NLR and A beta 42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.
Filiaciones:
Jacobs, T:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Jacobson, SR:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
VA Boston Healthcare Syst, VA Boston Cooperat Studies Program, MAVERIC, Boston, MA 02130 USA
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, Dept Neurol,St Pau Mem Unit, Barcelona, Spain
Berger, JS:
NYU, Dept Med, Div Cardiol, Grossman Sch Med, New York, NY USA
NYU, Dept Med, Div Hematol, Grossman Sch Med, New York, NY USA
Vedvyas, A:
NYU, Grossman Sch Med, Dept Neurol, New York, NY USA
Marsh, K:
NYU, Grossman Sch Med, Dept Neurol, New York, NY USA
He, TS:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Gutierrez-Jimenez, E:
Aarhus Univ, Inst Clin Med, Aarhus, Denmark
Fillmore, NR:
VA Boston Healthcare Syst, VA Boston Cooperat Studies Program, MAVERIC, Boston, MA 02130 USA
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA
Gonzalez, M:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Figueredo, L:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Gaggi, NL:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Plaska, CR:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Nathan S Kline Inst Psychiat Res, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA
Pomara, N:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Nathan S Kline Inst Psychiat Res, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA
NYU, Grossman Sch Med, Dept Pathol, New York, NY USA
Blessing, E:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Betensky, R:
NYU, Grossman Sch Med, Dept Neurol, New York, NY USA
Rusinek, H:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
NYU, Grossman Sch Med, Dept Radiol, New York, NY USA
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England
UK Dementia Res Inst UCL, London, England
Hong Kong Ctr Neurodegenerat Dis, Clear Water Bay, Hong Kong, Peoples R China
Univ Wisconsin Sch Med & Publ Hlth, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA
Blennow, K:
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Univ Gothenburg, Inst Neurosci & Physiol, Molndal, Sweden
Sorbonne Univ, Pitie Salpetriere Hosp, Paris Brain Inst, ICM, Paris, France
Univ Sci & Technol China, Div Life Sci & Med, Inst Aging & Brain Disorders, Neurodegenerat Disorder Res Ctr, Hefei, Peoples R China
Univ Sci & Technol China, Inst Aging & Brain Disorders, Dept Neurol, Hefei, Peoples R China
First Affiliated Hosp USTC, Hefei, Peoples R China
Glodzik, L:
NYU, Grossman Sch Med, Dept Neurol, New York, NY USA
Weill Cornell Med, Brain Hlth Imaging Inst, Dept Radiol, New York, NY USA
Wisniweski, TM:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
NYU, Grossman Sch Med, Dept Neurol, New York, NY USA
NYU, Grossman Sch Med, Dept Pathol, New York, NY USA
de Leon, MJ:
Weill Cornell Med, Brain Hlth Imaging Inst, Dept Radiol, New York, NY USA
NYU, Ctr Brain Hlth, Grossman Sch Med, New York, NY USA
Osorio, RS:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
Nathan S Kline Inst Psychiat Res, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA
Ramos-Cejudo, J:
NYU, Grossman Sch Med, Dept Psychiat, Div Brain Aging, 145 East 32nd St, New York, NY 10016 USA
VA Boston Healthcare Syst, VA Boston Cooperat Studies Program, MAVERIC, Boston, MA 02130 USA
Green Published, gold
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