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Short dental implants are an alternative to surgical bone augmentation procedures and longer implant placements. The high predictability of short dental implants has encouraged clinicians to load them immediately. However, there are few studies assessing the influence of immediate versus delayed loading of short (8 mm) dental implants. The purpose of this retrospective study was to report the midterm outcomes (survival and marginal bone loss) of immediate versus delayed loading of short (8 mm) implants. A total of 44 patients with 149 short implants fulfilled the inclusion criteria (95 and 54 implants with delayed and immediate loading, respectively). The descriptive clinical variables of implant survival, marginal bone loss, and prosthetic complications were recorded and statistically analyzed during the follow-up period. The mean follow-up time was 60 ± 40 months. The overall cumulative implant survival was 95.6%, and marginal bone loss was -0.1 ± 0.7 mm. No statistically significant differences were detected between the immediate and delayed loading groups in terms of implant survival (92.6% vs 97.5%) or marginal bone loss (-0.2 ± 0.8 mm vs -0.1 ± 0.7 mm), respectively. According to the results of this study, the immediate loading of short dental implants demonstrated predictability after midterm follow-up time. These results must be confirmed in future prospective studies.

[Background]: ApoJ/clusterin is a multifunctional protein highly expressed in the brain. The implication of ApoJ in βamyloid (Aβ) fibrillization and clearance in the context of Alzheimer’s disease has been widely studied, although the source and concentration of ApoJ that promotes or inhibits Aβ cerebral accumulation is not clear yet. ApoJ is abundant in plasma and approximately 20% can appear bound to HDL-particles. In this regard, the impact of plasmatic ApoJ and its lipidation status on cerebral.β-amyloidosis is still not known. Hence, our main objective was to study the effect of a peripheral increase of free ApoJ or reconstituted HDL particles containing ApoJ in an experimental model of cerebral βamyloidosis., [Methods]: Fourteen-month-old APP23 transgenic mice were subjected to subchronic intravenous treatment with rHDLrApoJ nanodiscs or free rApoJ for 1 month. Aβ concentration and distribution in the brain, as well as Aβ levels in plasma and CSF, were determined after treatments. Other features associated to AD pathology, such as neuronal loss and neuroinflammation, were also evaluated., [Results]: Both ApoJ-based treatments prevented the Aβ accumulation in cerebral arteries and induced a decrease in total brain insoluble Aβ42 levels. The peripheral treatment with rApoJ also induced an increase in the Aβ40 levels in CSF, whereas the concentration remained unaltered in plasma. At all the endpoints studied, the lipidation of rApoJ did not enhance the protective properties of free rApoJ. The effects obtained after subchronic treatment with free rApoJ were accompanied by a reduction in hippocampal neuronal loss and an enhancement of the expression of a phagocytic marker in microglial cells surrounding Aβ deposits. Finally, despite the activation of this phagocytic phenotype, treatments did not induce a global neuroinflammatory status. In fact, free rApoJ treatment was able to reduce the levels of interleukin-17 (IL17) and keratinocyte chemoattractant (KC) chemokine in the brain., [Conclusions]: Our results demonstrate that an increase in circulating human rApoJ induces a reduction of insoluble Aβ and CAA load in the brain of APP23 mice. Thus, our study suggests that peripheral interventions, based on treatments with multifunctional physiological chaperones, offer therapeutic opportunities to regulate the cerebral Aβ load., This work has been funded by Instituto de Salud Carlos III (ISCIII) [PI17/00275, PI14/01134, and PI13/00364], co-financed by the European Regional Development Fund (FEDER), and Fundació La Marató de TV3 [40/U/2014]. The Neurovascular Research Laboratory is part of the INVICTUS+ network, ISCIII, Spain [RD16/0019/0021]. J.L.S-Q is a member of the CIBER of Diabetes and Metabolism (CIBERDEM), ISCIII, Spain. M.H-G is supported by the Miguel Servet programme, ISCIII, Spain [CPII17/00010]. ICN2 acknowledges the support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Programme, under Grant SEV-2013-0295.

Intracerebral hemorrhage (ICH) is a devastating form of stroke and depending on the underlying cause, primary ICH is mainly caused by hypertension (HTN-ICH) or cerebral amyloid angiopathy (CAA-ICH). Currently, neuroimaging markers are required to identify the pattern for each etiology. The discovery of new biomarkers to improve the management of this pathology is therefore needed.A microarray analysis was carried out to analyze gene expression differences in blood samples from patients (1.5 months since the last ICH event) who suffered a CAA-ICH and HTN-ICH, and controls. The results were replicated by quantitative polymerase chain reaction and the plasma protein level of the best candidate was measured with enzyme-linked immunosorbent assay.The microarray analysis and the validation study revealed an increase in Golgin A8 Family, Member A (GOLGA8A) mRNA and protein levels in ICH cases compared to controls (P .01), although no differences were found between specific ICH etiologies. GOLGA8A plasma levels were also associated with the presence of multiple hemorrhages (P .05).The GOLGA8A level was increased in the blood of patients who suffered a primary ICH. We did not, however, find any candidate biomarker that distinguished CAA-ICH from HTN-ICH. The role of GOLGA8A in this fatal disorder has yet to be determined.

International audience; Amyloid-β (Aβ) accumulation in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) is likely caused by the impairment of its brain clearance that partly occurs through the blood-brain barrier (BBB). In this context, an in vitro BBB model is a valuable tool for studying the molecular mechanisms that regulate this process. This study assessed brain Aβ elimination across the BBB and its modulation by the natural chaperones Apolipoprotein A1 (ApoA1) and Apolipoprotein J/Clusterin (ApoJ). The model was based on primary cerebral endothelial cells that were cultured on Matrigel-coated Transwells and treated with fluorescently labeled-Aβ1-40 to track its efflux across the BBB, which corresponds to trafficking from the basolateral (brain) to apical (blood) compartments. We observed that the transport of basolateral Aβ1-40 was enhanced when it was complexed to rApoJ, whereas the complex formed with rApoA1 did not influence Aβ1-40 efflux. However, the presence of rApoA1 in the apical compartment was able to mobilize Aβ1-40 from the basolateral side. We also observed that both rApoA1 and rApoJ moderately crossed the monolayer (from blood to brain) through a mechanism involving the LDL receptor-related protein family. In contrast to the increased rApoJ efflux when complexed to Aβ1-40, rApoA1 trafficking was restricted when it was bound to the Aβ peptide. In summary, the present study highlights the role of ApoJ and ApoA1 in the in vitro modulation of Aβ elimination across the BBB.

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p

Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)–related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD). For this purpose, we produced and characterized human recombinant ApoA-I-wild type and ApoA-I-M proteins. Both of them were able to avoid the aggregation of Aβ in vitro, even though recombinant ApoA-I-M was significantly more effective in protecting endothelial cells from Aβ(1–42)-toxicity. Next, we determined the effect of chronic intravenous administration of rApoA-I-M in the APP23-transgenic mouse model of AD. We found reduced cerebral Aβ levels in mice that received rApoA-I-M, which were accompanied by a lower expression of astrocyte and microglia neuroinflammatory markers. Our results suggest an applicability of this molecule as a therapeutic candidate for protecting the brain in AD.