Abstract
BackgroundDendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer’s disease (AD), as suggested by prior in vitro studies. With the intent to investigate the clinical relevance of DC modifications in vivo, the present study was aimed to evaluate the levels of blood DCs in AD patients, in relation to the progression of the disease, the severity of its symptoms, and the treatment with acetylcholinesterase inhibitors (AChEIs), a class of drugs used to improve cognitive functioning in people with dementia.MethodsThe two main subpopulations of immature blood DCs, namely myeloid (mDCs) and plasmacytoid (pDCs) cells, were evaluated by flow cytometry analysis in 106 AD patients, in comparison with the same cells from 65 individuals with mild cognitive impairment (MCI) and 73 healthy control subjects (HC). The relationship between blood DC levels and symptom severity was also assessed in AD patients, and their blood DC frequency was considered both in the absence or presence of treatment with AChEIs.ResultsA significant depletion in blood mDCs was observed in AD patients, as compared to HC and MCI subjects. At variance, pDC levels were comparable among the three groups of subjects. The mDC decrease was evident only after the emergence of AD clinical symptoms, as confirmed by the follow-up analysis of a subgroup of MCI subjects who exhibited a significant decline in mDCs after their conversion to AD. Notably, the mDC decline was inversely correlated in AD patients with the frequency and severity of depressive symptoms. Eventually, the mDC depletion was not observable in patients treated with AChEIs.ConclusionsOur results provide the first evidence that blood mDC levels are dysregulated in AD. This phenomenon appears mainly linked to AD progression, associated with stronger severity of AD-related symptoms, and influenced by AChEI treatment. Taken all together, these data suggest that blood mDCs may serve as a cell source to test disease-induced and treatment-related changes and support the innovative notion that DCs play a role in AD, as ultimate evidence of the immune system participation in disease progression.
Highlights
Dendritic cells (DCs) are major orchestrators of immune responses and inflammation
We previously described that monocyte-derived DCs from Alzheimer’s disease (AD) patients show a more pronounced proinflammatory profile than DCs obtained from healthy control (HC) subjects [3]
Results mDC percentage is decreased in peripheral blood from AD patients as compared to mild cognitive impairment (MCI) and healthy control subjects (HC) subjects We firstly investigated by flow cytometry the relative proportion of peripheral blood DC subsets, mDCs and pDCs, in the three main groups of subjects, namely HC, MCI, and AD
Summary
Dendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer’s disease (AD), as suggested by prior in vitro studies. In association with amyloid plaques, reactive microglia have been broadly observed in AD brain. These cells are considered the resident mononuclear phagocytes, which act as the first line of brain defense, like macrophages in the periphery, and are associated with the release of many inflammatory factors in AD brains, such as complement factors, pro-inflammatory cytokines and chemokines [1]. Pro-inflammatory mediators (mainly cytokines and chemokines) are increased outside the CNS of AD patients and in particular in their peripheral blood [2]. Monocytes obtained from AD patients have a limited potential to differentiate into macrophages, which, in turn, show an impaired phagocytosis of amyloid β (Aβ) [5]
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