Protective Role of Cerebrospinal Fluid Inflammatory Cytokines in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer’s Disease Carrying Apolipoprotein E4 Genotype

Article type: Research Article

Authors: Motta, Caterina^{a; b; *} | Finardi, Annamaria^c | Toniolo, Sofia^b | Di Lorenzo, Francesco^b | Scaricamazza, Eugenia^b | Loizzo, Stefano^d | Mercuri, Nicola Biagio^b | Furlan, Roberto^c | Koch, Giacomo^a | Martorana, Alessandro^b

Affiliations: [a] Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy | [b] Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy | [c] Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of Experimental Neurology (InSpe), San Raffaele Scientific Institute, Milan, Italy | [d] Center for Global Health, Italian National Institute of Health, Rome, Italy

Correspondence: [*] Correspondence to: Caterina Motta, MD, Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy. Tel.: +39 0651501181; E-mail: c.motta@hsantalucia.it.

Abstract: Background:Neuroinflammatory cytokines can play a pivotal role in Alzheimer’s disease (AD) contributing to the evolution of degenerative processes. Objective:We aimed at evaluating the levels of cerebrospinal fluid (CSF) inflammatory cytokines, chemokines, and growth factors in subjects with diagnosis of amnestic mild cognitive impairment and mild AD. Methods:We evaluated CSF contents of inflammatory cytokines in 66 patients divided according to the NIA-AA research framework and the APOE genotype. CSF of a group of cognitively unimpaired individuals (n = 23) was evaluated as control. All patients were evaluated for 24 months using Mini-Mental State Examination (MMSE). Results:We found significant increased levels of IL-4, IL-6, IL-8, and G-CSF in the CSF of A+/T–APOE4 carriers, respect to A+/T–patients homozygous for APOE3, respect to A+/T+ patients, regardless the APOE status, and respect to controls. Over a period of 24 months, A+/T–APOE4 carriers, with increased levels of cytokines, showed a preserved cognitive evaluation when compared to the other subgroups of patients (delta MMSE at 24 months respect to baseline: 0.10±0.35; p < 0.05). Conclusion:Our data suggest that during early phases of AD, in APOE4 carriers, Aβ pathology likely induces a specific cytokines pattern synthesis associated to cognitive preservation. These data highlight the different role that neuroinflammation can play in AD pathology based on the presence of specific CSF biomarkers and on the APOE status.

Keywords: Amyloid-β 42, APOE , cognitive decline, G-CSF, interleukins, tau

DOI: 10.3233/JAD-191250

Journal: Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 681-689, 2020