TY - JOUR
T1 - Protective Role of Cerebrospinal Fluid Inflammatory Cytokines in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease Carrying Apolipoprotein E4 Genotype
AU - Motta, Caterina
AU - Finardi, Annamaria
AU - Toniolo, Sofia
AU - Di Lorenzo, Francesco
AU - Scaricamazza, Eugenia
AU - Loizzo, Stefano
AU - Mercuri, Nicola Biagio
AU - Furlan, Roberto
AU - Koch, Giacomo
AU - Martorana, Alessandro
N1 - Publisher Copyright:
© 2020 - IOS Press and the authors. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Amyloid-β 42
KW - APOE
KW - cognitive decline
KW - G-CSF
KW - interleukins
KW - tau
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U2 - 10.3233/JAD-191250
DO - 10.3233/JAD-191250
M3 - Article
C2 - 32538836
AN - SCOPUS:85088846037
VL - 76
SP - 681
EP - 689
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 2
ER -