Abstract
Amnestic mild cognitive impairment (aMCI) conversion to Alzheimer’s disease (AD) is seen in a sizable portion of aMCI patients; correlates predicting such conversion are poorly defined but neuroinflammation and the reactivation of chronic viral infections are suspected to play a role in this phenomenon. We analyzed these aspects in two homogeneous groups of aMCI who did or did not convert to AD over a 24-months period. Results showed that at baseline in those aMCI individuals who did not convert to AD: 1) Aβ1-42 stimulated production of the pro-inflammatory cytokines IL6 and IL1β by CD14+ cells was significantly reduced (p = 0.01), 2) CD14+/IL-33+ cells were increased (p = 0.0004); 3) MFI of TLR8 and TLR9 was significantly increased, and 4) better preserved hippocampus volumes were observed and correlated with IL33+/CD14+ cells. Notably, Aβ1-42 stimulated production of the antiviral cytokine IFN-λ was increased as well in non-AD converters, although with a borderline statistical significance (p = 0.05). Data herein indicating that proinflammatory cytokines are reduced, whereas IFN-λ production and TLR8 and 9 MFI are augmented in those aMCI in whom AD conversion is not observed suggest that the ability to mount stronger antiviral response within an antiiflammatory milieu associates with lack of AD conversion.
Highlights
Mild cognitive impairment (MCI) is defined as a subjective and objective decline in cognitive performance that is greater than expected for an individual’s age and education level, but does not meet criteria for the diagnosis of dementia[1,2,3]
No differences were observed in gender, age, years of education, global cognitive levels (MMSE) and ApoE4 status when Alzheimer’s disease (AD) converters and AD non-converters were compared at baseline
CD14+ immune cells of AD converters and AD non-converters were either unstimulated or stimulated with TLR8 and 9 agonists (ODN and single-stranded RNA oligonucleotide (ssRNA), respectively), and the percentage of toll like receptors (TLR)-expressing cells was examined by flow-cytometry
Summary
Mild cognitive impairment (MCI) is defined as a subjective and objective decline in cognitive performance that is greater than expected for an individual’s age and education level, but does not meet criteria for the diagnosis of dementia[1,2,3]. Not suitable for defining preclinical AD-stage if considered as unique index, this downstream topological biomarker is adequate for the screening of subjects at risk, as recently stressed[19] The validity of these results is hampered by the fact that most of published studies utilized a single marker to predict progression to AD9,10,14–16 even if this phenomenon is multifactorial. Such multidimensionality,is reflected in the observation that a combination of MRI (hippocampal volumes)[14,15,16], genetic (ApoE)[20] and humoral (CSF levels of beta amyloid and phosporylated τ protein)[11,12,13] indexes is currently suggested to have the greatest predictive value toward AD conversion. We analyzed one of the MRI biomarker of AD-associated neural injury, the hippocampal volume
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