IMPORTANCE Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD.OBJECTIVE To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing. DESIGN, SETTING, AND PARTICIPANTSThis case-control study included 32 participants recruited from the Charles F.

In this study we evaluated the relationship between amphetamine-induced behavioral alterations and dopamine release and uptake characteristics in Fmr1 knockout (Fmr1 KO) mice, which model fragile X syndrome. The behavioral analyses, obtained at millisecond temporal resolution and 2 mm spatial resolution using a force-plate actometer, revealed that Fmr1 KO mice express a lower degree of focused stereotypy compared to wild type (WT) control mice after injection with 10 mg/kg (ip) amphetamine. To identify potentially related neurochemical mechanisms underlying this phenomenon, we measured electrically-evoked dopamine release and uptake using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal brain slices. At 10 weeks of age, dopamine release per pulse, which is dopamine release corrected for differences in uptake, was unchanged. However, at 15 (the age of behavioral testing) and 20 weeks of age, dopamine per pulse and the maximum rate of dopamine uptake was diminished in Fmr1 KO mice compared to WT mice. Dopamine uptake measurements, obtained at different amphetamine concentrations, indicated that dopamine transporters in both genotypes have equal affinities for amphetamine. Moreover, dopamine release measurements from slices treated with quinpirole, a D2-family receptor agonist, rule out enhanced D2 autoreceptor sensitivity as a mechanism of release inhibition. However, dopamine release, uncorrected for uptake and normalized against the corresponding pre-drug release peaks, increased in Fmr1 KO mice, but not in WT mice. Collectively, these data are consistent with a scenario in which a decrease in extracellular dopamine levels in the striatum result in diminished expression of focused stereotypy in Fmr1 KO mice.

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Purpose: To determine the presence and characterize location of retinal vascular lesions in patients with hereditary hemorrhagic telangiectasia. Design: Prospective cross-sectional pilot descriptive study. Participants: Eighteen patients (age 22 to 65) with a clinical diagnosis of hereditary hemorrhagic telangiectasia. Methods: Patients completed the Visual Function Questionnaire-25 and underwent a single study visit with dilated ophthalmic examination, optical coherence tomography angiography (OCTA) and fluorescein angiography (FA) with widefield imaging. Main Outcome Measures: Presence of retinal vascular abnormalities in 1 or more quadrants identified on widefield FA, VFQ-25 scores, retinal vessel architecture on FA and OCTA, and dilated ophthalmic exam findings. Results: Of the 18 patients recruited, fine telangiectatic vessels with capillary dilation and tortuosity were identified in 78% by FA imaging. Conclusions: In the first FA and OCTA analysis of the retina of unrelated HHT subjects, we found a high rate of temporal and nasal telangiectasias. These telangiectasias were more apparent