Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer's continuum.

BACKGROUND: Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer's disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown. OBJECTIVE: We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors. METHODS: The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer's continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aß42, Aß40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aß status (positivity defined as Aß42/40 < 0.071). RESULTS: The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aß positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aß negative participants. CONCLUSIONS: Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer's continuum.

Genetic Predisposition to Alzheimer's Disease Is Associated with Enlargement of Perivascular Spaces in Centrum Semiovale Region.

This study investigated whether genetic factors involved in Alzheimer's disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed based on a validated visual rating scale. We used univariate and multivariate logistic regression models to investigate associations between ePVS in BG and CS with BIN1-rs744373, as well as APOE genotypes. We found a significant association of the BIN1-rs744373 polymorphism in the CS subscale (p value = 0.019; OR = 2.564), suggesting that G allele carriers have an increased risk of ePVS in comparison with A allele carriers. In stratified analysis by APOE-ε4 status (carriers vs. non-carriers), these results remained significant only for ε4 carriers (p value = 0.011; OR = 1.429). To our knowledge, the present study is the first suggesting that genetic predisposition for AD is associated with ePVS in CS. These findings provide evidence that underlying biological processes affecting AD may influence CS-ePVS.

Endovascular treatment of unruptured and ruptured brain arteriovenous malformations with Onyx18: a monocentric series of 84 patients.

BACKGROUND: Brain arteriovenous malformations (AVMs) are a rare pathology, and their treatment is discussed. The development of techniques and materials in endovascular, radiosurgical, and neurosurgical fields led to higher rates of complete occlusions and good clinical outcomes. MATERIALS AND METHODS: 84 patients (52 men, 32 women; mean age 38.2 years; range, 9-70 years) were treated at our institution with Onyx18 from 2001 to 2011. Patients treated with other embolic agents, with micro-AVMs, were not included in the analysis. RESULTS: Complete occlusion was achieved in 27/84 patients (32.2%), in 40/84 (47.6%) brain AVMs occlusion of 80-90% of the nidus was obtained, and in 17/84 (20.3%) cases <80% of the nidus was occluded. Intraprocedural adverse events occurred in 11/84 patients (13.1%), and overall mortality and disabling permanent morbidity were 2.3% (2/84) and 4.7% (4/84), respectively. CONCLUSIONS: Endovascular treatment may be considered a safe and effective approach in superficial small brain AVMs in addition to surgery, mostly in ruptured AVMs. The therapeutic strategy should be to cure small and medium AVMs with endovascular treatment alone or combined treatment. Large unruptured AVMs (Spetzler-Martin grades IV-V) should be treated with target embolization of high flow fistulas or intranidal aneurysms.