Apolipoprotein E (ApoE) has become a primary focus of research after the discovery of its strong linkage to Alzheimer’s disease (AD), where the ApoE4 variant is the highest genetic risk factor for this disease. ApoE is commonly found in amyloid deposits of different origins, and its interaction with amyloid-β peptide (Aβ), the hallmark of AD, is well known. However, studies on the interaction of ApoEs with other amyloid-forming proteins are limited. Islet amyloid polypeptide (IAPP) is an amyloid-forming peptide linked to the development of type-2 diabetes and has also been shown to be involved in AD pathology and vascular dementia. Here we studied the impact of ApoE on IAPP aggregation and IAPP-induced toxicity on blood vessel pericytes. Using both in vitro and cell-based assays, we show that ApoE efficiently inhibits the amyloid formation of IAPP at highly substoichiometric ratios and that it interferes with both nucleation and elongation. We also show that ApoE protects the pericytes against IAPP-induced toxicity, however, the ApoE4 variant displays the weakest protective potential. Taken together, our results suggest that ApoE has a generic amyloid-interfering property and can be protective against amyloid-induced cytotoxicity, but there is a loss of function for the ApoE4 variant.

Amyloid-formation by the islet amyloid polypeptide (IAPP), produced by the β-cells in the human pancreas, has been associated with the development of type II diabetes mellitus (T2DM). The human plasma-protein transthyretin (TTR), a well-known amyloid-inhibiting protein, is interestingly also expressed within the IAPP producing β-cells. In the present study, we have characterized the ability of TTR to interfere with IAPP amyloid-formation, both in terms of its intrinsic stability as well as with regard to the effect of TTR-stabilizing drugs. The results show that TTR can prolong the lag-phase as well as impair elongation in the course of IAPP-amyloid formation. We also show that the interfering ability correlates inversely with the thermodynamic stability of TTR, while no such correlation was observed as a function of kinetic stability. Furthermore, we demonstrate that the ability of TTR to interfere is maintained also at the low pH environment within the IAPP-containing granules of the pancreatic β-cells. However, at both neutral and low pH, the addition of TTR-stabilizing drugs partly impaired its efficacy. Taken together, these results expose mechanisms of TTR-mediated inhibition of IAPP amyloid-formation and highlights a potential therapeutic target to prevent the onset of T2DM.

The Vertigo Symptom Scale - short form (VSS-SF) is commonly used to measure dizziness and vertigo over the past month. This study aimed to (1) adapt the VSS-SF for the Swedish population and assess its psychometric properties, and (2) develop a modified version for measuring symptoms in the acute phase of acute vestibular syndrome (AVS). The VSS-SF was translated into Swedish and adapted cross-culturally. Its psychometric properties were evaluated in 86 AVS patients, both in the acute stage (1-7 days from symptom onset) with a modified acute version, and after six weeks of vestibular rehabilitation using the standard VSS-SF. Factor structure, convergent and discriminant validity, and internal consistency were analyzed. Test-retest reliability was assessed at six weeks. Participants were also evaluated with the Dizziness Handicap Inventory (DHI) and balance tests. Controls included 54 healthy participants. Exploratory factor analysis revealed a two-factor structure for both versions, corresponding to vertigo-balance (VSS-V) and autonomic-anxiety (VSS-A) subscales. Both versions demonstrated strong factor structures with adequate loadings. Internal consistency was high for the standard version (Cronbach's alpha 0.76 to 0.87) and for the total and VSS-V subscale of the acute version (0.82 and 0.85, respectively), but poor for the acute VSS-A subscale (0.50). Convergent validity was supported by Spearman's rank correlations. The discriminative ability was excellent for the acute VSS-SF and VSS-V (AUC 0.98 and 0.99), and acceptable for VSS-A (AUC 0.77). After six weeks, discriminative ability decreased but remained above 0.5. Test-retest reliability at six weeks was excellent for all scales (ICC 0.94, 0.93, and 0.93 for VSS-SF, VSS-V, and VSS-A). The VSS-SF was successfully adapted for the Swedish population, including an acute version for early dizziness assessment. Both versions confirmed a robust two-factor structure, with the acute version showing excellent early discriminative ability, particularly for the vertigo-balance dimension. However, the autonomic-anxiety subscale showed weaker psychometric properties, suggesting limited suitability for AVS patients. The adapted scales show promise for clinical use in diagnosing and evaluating dizziness and vertigo in the Swedish population. Clinicaltrials.gov Identifier NCT05056324, September 24, 2021. https://clinicaltrials.gov/ct2/show/NCT05056324.

Background: Acute vestibular syndrome (AVS) causes sudden and continuous vertigo, dizziness, and postural instability and is a common reason for emergency department visits, most commonly due to vestibular neuritis and, in rare cases, stroke. Vestibular rehabilitation (VR) is an evidence-based exercise therapy that facilitates vestibular compensation and is effective in chronic vestibular disorders. However, evidence for VR in acute vertigo remains limited and, despite guideline support, it remains underused in practice. Internet-based VR has demonstrated benefit in chronic dizziness but has not been evaluated in acute vertigo. This study aimed to evaluate the efficacy of an internet-based VR tool compared with standard care (written instructions) in reducing vestibular symptoms after acute onset vertigo. Methods and Findings: A multicentre, randomised, evaluator-blinded superiority trial was conducted across nine hospitals in Sweden. Adults with ongoing AVS were recruited within 1–7 days after symptom onset and randomised (1:1) to six weeks of internet-based VR with personalised, progressively adjusted home exercises or to written instructions for home-based VR exercises. The primary outcome was the between-group difference in vestibular symptoms at six weeks measured using the Vertigo Symptom Scale Short Form (VSS-SF; range 0–60), with a difference of ≥3 points prespecified as clinically significant. Secondary outcomes included dizziness-related disability, walking speed, and balance. Of 184 randomised participants, 183 were included in the analyses (94 online VR; 89 written instructions; median age 56 years). In the intention-to-treat analysis, both groups improved at six weeks, with no significant between-group difference (adjusted mean difference −2.0 points, 95% CI −4.9 to 0.9; p = 0.18). Per-protocol analyses were consistent (−1.7 points, 95% CI −4.7 to 1.3; p = 0.27). Over 12 weeks, both groups showed reduced vestibular symptoms and improved disability, balance, and walking speed, without significant between-group differences. No serious adverse events were attributed to the interventions, and compliance was high in both groups. Conclusions: Internet-based VR was not superior to written instructions in reducing vestibular symptoms six weeks after acute onset vertigo. Both groups demonstrated improvement from baseline, with no statistically significant between-group differences. These findings suggest that ensuring access to vestibular rehabilitation exercises may be more important than the specific mode of delivery after acute onset vertigo, and internet-based tools represent viable alternatives for patients who prefer or may benefit from a digital format. Trial registration: Clinicaltrials.gov NCT05056324. https://clinicaltrials.gov/study/NCT05056324 . Registered on September 24, 2021.