Association between anxiety symptoms and Alzheimer's disease biomarkers in cognitively healthy adults: A systematic review and meta-analysis.

OBJECTIVE: Anxiety has been identified as both a risk factor and prodromal symptom for Alzheimer's disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta-analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropathology: amyloid-beta (Aß) and tau. METHODS: Systematic literature searches were conducted across 5 databases. Studies investigating the relationship between anxiety and AD neuropathology (i.e., Aß and/or tau) in cognitively healthy adults were eligible. Where possible, effect sizes were combined across studies, for Aß and tau separately, using random-effects meta-analyses. Sensitivity analyses were performed to assess whether results differed according to anxiety type (i.e., state and trait) and biomarker assessment modality (i.e., positron emission tomography and cerebrospinal fluid). RESULTS: Twenty-seven studies reporting data from 14 unique cohorts met eligibility criteria. Random-effects meta-analyses revealed no associations between self-reported anxiety symptoms and either Aß (13 studies, Fisher's z = 0.02, 95% confidence interval [CI] -0.01-0.05, p = 0.194) or tau (4 studies, Fisher's z = 0.04, 95% CI -0.02-0.09, p = 0.235). Results remained unchanged across sensitivity analyses. CONCLUSIONS: In cognitively healthy adults, meta-analytic syntheses revealed no associations between anxiety symptoms and either Aß or tau. There is a critical need, however, for larger studies with follow-up periods to examine the effect of anxiety symptom onset, severity, and chronicity on AD neuropathology. Additionally, further research investigating other potential neurobiological correlates is crucial to advance scientific understanding of the relationship between anxiety and dementia.

Mammalian Cells Exocytose Alkylated Gold Nanoparticles via Extracellular Vesicles.

Understanding the exocytosis of nanoparticles (NPs) from cells is valuable because it informs design rules of NPs that support desirable cellular retention for nanomedicine applications, but investigations into the mechanism for the exocytosis of NPs remain scarce. We elucidate the mechanism for the exocytosis of dodecyl-terminated, polyethylene glycol-coated gold NPs (termed "dodecyl-PEG-AuNP"). The Au core enables ultrastructural differentiation of the exocytosed NPs from the nearby extracellular vesicles (EVs). The PEG shell prevents interparticle agglomeration or aggregation that disfavors exocytosis. The minute amounts of alkyl chains on the PEG shell not only promote cellular uptake but also improve exocytosis by up to 4-fold higher probability and upregulate exocytosis- and vesicle-related genes. After entering Kera-308 keratinocytes and trafficking to multivesicular bodies and lysosomes, these NPs exit the cell predominantly via unconventional exocytosis, accompanied by enhanced secretion of sub-100 nm, CD81-enriched exosomes. The pathway for NP exocytosis and subpopulation of EVs that are secreted alongside the exocytosed NPs depends on dodecyl loading. This work provides insights into dissecting the mechanism of NP exocytosis and its relationship with EV secretion.

Autism traits in individuals with agenesis of the corpus callosum.

Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n = 106) with the Autism Spectrum Quotient (AQ) and found that 45 % of children, 35 % of adolescents, and 18 % of adults exceeded the predetermined autism-screening cut-off. Interestingly, performance on the AQ's imagination domain was inversely correlated with magnetoencephalography measures of resting-state functional connectivity in the right superior temporal gyrus. Individuals with AgCC should be screened for ASD and disorders of the corpus callosum should be considered in autism diagnostic evaluations as well.