PMID- 26811068 OWN - NLM STAT- MEDLINE DCOM- 20161006 LR - 20181113 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 13 DP - 2016 Jan 25 TI - Myeloid dendritic cells are decreased in peripheral blood of Alzheimer's disease patients in association with disease progression and severity of depressive symptoms. PG - 18 LID - 10.1186/s12974-016-0483-0 [doi] LID - 18 AB - BACKGROUND: 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. 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. METHODS: The 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. RESULTS: A 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. CONCLUSIONS: Our 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. FAU - Ciaramella, Antonio AU - Ciaramella A AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. a.ciaramella@hsantalucia.it. FAU - Salani, Francesca AU - Salani F AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. f.salani@hsantalucia.it. FAU - Bizzoni, Federica AU - Bizzoni F AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. f.bizzoni@hsantalucia.it. FAU - Orfei, Maria Donata AU - Orfei MD AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. md.orfei@hsantalucia.it. FAU - Caltagirone, Carlo AU - Caltagirone C AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. c.caltagirone@hsantalucia.it. AD - Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. c.caltagirone@hsantalucia.it. FAU - Spalletta, Gianfranco AU - Spalletta G AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. g.spalletta@hsantalucia.it. AD - Neuropsychology Unit, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. g.spalletta@hsantalucia.it. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA. g.spalletta@hsantalucia.it. FAU - Bossu, Paola AU - Bossu P AD - Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Experimental Neuro-psychobiology Lab, Via Ardeatina 306, 00179, Rome, Italy. p.bossu@hsantalucia.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160125 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (HLA-DR Antigens) SB - IM MH - Aged MH - Alzheimer Disease/*complications/*pathology MH - Cognitive Dysfunction/etiology MH - Dendritic Cells/*pathology MH - Depression/*etiology MH - Disease Progression MH - Female MH - HLA-DR Antigens/metabolism MH - Humans MH - Italy MH - Male MH - Myeloid Cells/*pathology MH - Neuropsychological Tests MH - Psychiatric Status Rating Scales PMC - PMC4727381 EDAT- 2016/01/27 06:00 MHDA- 2016/10/08 06:00 PMCR- 2016/01/25 CRDT- 2016/01/27 06:00 PHST- 2015/07/27 00:00 [received] PHST- 2016/01/16 00:00 [accepted] PHST- 2016/01/27 06:00 [entrez] PHST- 2016/01/27 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] PHST- 2016/01/25 00:00 [pmc-release] AID - 10.1186/s12974-016-0483-0 [pii] AID - 483 [pii] AID - 10.1186/s12974-016-0483-0 [doi] PST - epublish SO - J Neuroinflammation. 2016 Jan 25;13:18. doi: 10.1186/s12974-016-0483-0.