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The article discusses research conducted to investigate the interaction of the Apolipoprotein E (ApoE) genotype and angiotensin converting enzyme (ACE) inhibitors in Alzheimer's disease. Researchers evaluated 355 patients. They found that ApoE4 carriers treated with ACE inhibitors had more diagnoses of AD than those who did not, that ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele and that the effects of ACE inhibitors on AD may be different depending on ApoE genotype.

We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37–0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49–0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35–2.79]), and correlated with all neuropsychological tests (r 's = 0.13–0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10–0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau. • Baseline plasma neurofilament light was higher in Alzheimer's disease dementia than mild cognitive impairment and normal cognition. • Baseline plasma neurofilament light was associated with baseline cognitive test score and predicted subsequent decline but did not predict diagnostic conversion. • Baseline plasma total tau was higher in Alzheimer's disease dementia than mild cognitive impairment and normal cognition. • There were no statistically significant effects for baseline plasma total tau on cognitive decline or diagnostic conversion. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) binds to clAP 1 and cIAP2 (clAP 1/2) and recruits them to the cytoplasmic domain of several members of the TNF receptor (TNFR) superfamily, including the TNF-TNFR1 ligand-receptor complex. Here, we define a cIAP1/2-interacting motif (CIM) within the TRAF-N domain of TRAF2, and we use TRAF2 CIM mutants to determine the role of TRAF2 and cLAP 1/2 individually, and the TRAF2-cIAP1/2 interaction, in TNFR1dependent signaling. We show that both the TRAF2 RING domain and the TRAF2 CIM are required to regulate NF-κB-inducing kinase stability and suppress constitutive noncanonical NF-κB activation. Conversely, following TNFR1 stimulation, cells bearing a CIM-mutated TRAF2 showed reduced canonical NF-κB activation and TNF-induced RIPK1 ubiquitylation. Remarkably, the RING domain of TRAF2 was dispensable for these functions. However, like the TRAF2 CIM, the RING domain of TRAF2 was required for protection against TNF-induced apoptosis. These results show that TRAF2 has anti-apoptotic signaling roles in addition to promoting NF-κB signaling and that efficient activation of NF-κB by TNFR1 requires the recruitment of cIAP1/2 by TRAF2. [ABSTRACT FROM AUTHOR]