Transparency Logs via Append-only Authenticated Dictionaries

Transparency logs allow users to audit a potentially malicious service, paving the way towards a more accountable Internet. For example, Certificate Transparency (CT) enables domain owners to audit Certificate Authorities (CAs) and detect impersonation attacks. Yet, to achieve their full potential, transparency logs must be bandwidth-efficient when queried by users. Specifically, everyone should be able to efficiently look up log entries by their key and efficiently verify that the log remains append-only. Unfortunately, without additional trust assumptions, current transparency logs cannot provide both small-sized lookup proofs and small-sized append-only proofs. In fact, one of the proofs always requires bandwidth linear in the size of the log, making it expensive for everyone to query the log. In this paper, we address this gap with a new primitive called an append-only authenticated dictionary (AAD). Our construction is the first to achieve (poly)logarithmic size for both proof types and helps reduce bandwidth consumption in transparency logs. This comes at the cost of increased append times and high memory usage, both of which remain to be improved to make practical deployment possible

Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults

BACKGROUND: Plasma neurofilament light (NfL) is an indicator of neurodegeneration and/or neuroaxonal injury in persons with Alzheimer's disease (AD) and a wide range of other neurological disorders. Here, we characterized and compared plasma NfL concentrations in cognitively unimpaired (CU) late-middle-aged and older adults with two, one, or no copies of the APOE ε4 allele, the major genetic risk factor for AD. We then assessed plasma NfL associations with brain imaging measurements of AD-related neurodegeneration (hippocampal atrophy and a hypometabolic convergence index [HCI]), brain imaging measurements of amyloid-β plaque burden, tau tangle burden and white matter hyperintensity volume (WMHV), and delayed and total recall memory scores. METHODS: Plasma NfL concentrations were measured in 543 CU 69 ± 9 year-old participants in the Arizona APOE Cohort Study, including 66 APOE ε4 homozygotes (HM), 165 heterozygotes (HT), and 312 non-carriers (NC). Robust regression models were used to characterize plasma NfL associations with APOE ε4 allelic dose before and after adjustment for age, sex, and education. They were also used to characterize plasma NfL associations with MRI-based hippocampal volume and WMHV measurements, an FDG PET-based HCI, mean cortical PiB PET measurements of amyloid-β plaque burden and meta-region-of-interest (meta-ROI) flortaucipir PET measurements of tau tangle burden, and Auditory Verbal Learning Test (AVLT) Delayed and Total Recall Memory scores. RESULTS: After the adjustments noted above, plasma NfL levels were significantly greater in APOE ε4 homozygotes and heterozygotes than non-carriers and significantly associated with smaller hippocampal volumes (r =  - 0.43), greater tangle burden in the entorhinal cortex and inferior temporal lobes (r = 0.49, r = 0.52, respectively), and lower delayed (r =  - 0.27), and total (r =  - 0.27) recall memory scores (p < 0.001). NfL levels were not significantly associated with PET measurements of amyloid-β plaque or total tangle burden. CONCLUSIONS: Plasma NfL concentrations are associated with the APOE ε4 allele, brain imaging biomarkers of neurodegeneration, and less good recall memory in CU late-middle-aged and older adults, supporting its value as an indicator of neurodegeneration in the preclinical study of AD

Data_Sheet_1_Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.pdf

IntroductionSeveral studies have suggested that greater adiposity in older adults is associated with a lower risk of Alzheimer’s disease (AD) related cognitive decline, some investigators have postulated that this association may be due to the protective effects of the adipose tissue-derived hormone leptin. In this study we sought to demonstrate that higher body mass indices (BMIs) are associated with greater baseline FDG PET measurements of the regional cerebral metabolic rate for glucose (rCMRgl), a marker of local neuronal activity, slower rCMRgl declines in research participants with amnestic mild cognitive impairment (aMCI). We then sought to clarify the extent to which those relationships are attributable to cerebrospinal fluid (CSF) or plasma leptin concentrations.Materials and methodsWe used baseline PET images from 716 73 ± 8 years-old aMCI participants from the AD Neuroimaging Initiative (ADNI) of whom 453 had follow up images (≥6 months; mean follow up time 3.3 years). For the leptin analyses, we used baseline CSF samples from 81 of the participants and plasma samples from 212 of the participants.ResultsAs predicted, higher baseline BMI was associated with greater baseline CMRgl measurements and slower declines within brain regions preferentially affected by AD. In contrast and independently of BMI, CSF, and plasma leptin concentrations were mainly related to less baseline CMRgl within mesocorticolimbic brain regions implicated in energy homeostasis.DiscussionWhile higher BMIs are associated with greater baseline CMRgl and slower declines in persons with aMCI, these associations appear not to be primarily attributable to leptin concentrations.</p