The relationship between familial amyloid polyneuropathy (FAP), which is caused by mutated transthyretin (TTR), and inflammation has only recently been noted. To determine whether inflammation is present in FAP carriers and patients, serum interleukin (IL)−6 concentration in 57 healthy donors (HD), 21 FAP carriers, and 66 FAP patients was examined, with the relationship between IL-6 and TTR assessed in each group by multiple regression analysis and structural equation models (SEM). Compared with HD, IL-6 concentration was elevated in FAP carriers (p = 0.001, 95% CI 0.398–1.571) and patients (p = 0.002, 95% CI 0.362–1.521). Further, SEM indicated a positive relationship between IL-6 and TTR in FAP carriers (p = 0.010, 95% CI 0.019–0.140), but not in HD and FAP patients. In addition, we determined whether TTR induces production of pro-inflammatory cytokines ex vivo. HD-derived CD14 + monocytes and induced pluripotent stem cell-derived myeloid lineage cells from a HD and FAP patient dose-dependently produced IL-6 under mutated and aggregated TTR conditions, compared with wild-type TTR. In conclusion, FAP carriers and patients are in an inflammatory state, with the presence of mutated TTR being a trigger of inflammation, especially in FAP carriers.

Immune-mediated necrotizing myopathy (IMNM) is accompanied by extramuscular manifestations including cardiac complications, and such cardiac complications have a serious prognostic impact on these patients. This study aims to investigate cardiac manifestations and the presence of anti-striational antibodies in patients with IMNM. We retrospectively analyzed 13 patients diagnosed with IMNM and measured anti-striational antibodies. We also reviewed the literature on cardiac involvement in patients with IMNM. In the present study, all patients had elevated serum troponin T levels, and 76.9 % of the cases had electrocardiographic or echocardiographic manifestations. Three patients (23.1 %) developed acute heart failure during the course of the study; one patient died. Anti-Kv1.4 antibodies were positive in 10 patients (83.3 %), and in addition to anti-Kv1.4 antibodies, anti-titin antibodies were detected in one fatal case. Our literature review also showed that cardiac involvement is common in IMNM, with arrhythmias and left ventricular diastolic dysfunction as the main findings. Hence, cardiac involvement in IMNM may be more frequent than generally recognized, and perhaps this extramuscular manifestation should be carefully monitored. Anti-striational antibodies, particularly anti-Kv1.4 antibodies, may be potential biomarkers of inflammatory cardiomyopathy associated with IMNM, and the presence of anti-striational antibodies may have a prognostic impact on patients' outcomes.

Background: The relationship between peripheral cytokines and neuroimaging biomarkers for Alzheimer's disease (AD) is not yet well established. Objective: To determine the association of cytokine plasma levels with brain amyloid deposition, cortical glucose metabolism, hippocampal volume, and white matter lesions (WMLs) in older adults with mild cognitive impairment (MCI). Methods: We recruited 50 older individuals with amnestic MCI (25 men and 25 women; median age, 75 years) and performed plasma analysis, ¹¹ C-Pittsburgh compound-B positron-emission tomography (PiB-PET), ¹⁸ F-fluorodeoxyglucose positron-emission tomography, and magnetic resonance imaging. Global PiB and fluorodeoxyglucose (FDG) uptake were assessed by the ratio of the voxel number-weighted average of the mean uptake in the frontal, temporoparietal, and posterior cingulate, in reference to the cerebellum. The Fazekas scale was used to evaluate WMLs. Plasma levels of 48 cytokines were simultaneously measured with bead-based multiplex assays. Results: The plasma levels of IL-2Ra, IL-3, IL-5, IL-7, IL-9, IL-16, IL-18, fibroblast growth factor (FGF-basic), granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein-1α (MIP-1α), regulated on activation, normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), cutaneous T-cell attracting chemokine (CTACK), growth-regulated oncogene α (GROα), hepatocyte growth factor (HGF), interferon-α2 (IFN-α2), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-3 (MCP-3), β-nerve growth factor (β-NGF), stem cell factor (SCF), stem cell growth factor-β (SCGF-β), and TNF-related apoptosis-inducing ligand (TRAIL) were significantly associated with global PiB uptake, whereas those of IL-7 and GROα were significantly associated with hippocampal volume after covariate adjustment and false discovery rate correction. Conclusions: Plasma cytokines are associated with brain amyloid deposition rather than brain dysfunction or hippocampal atrophy. Moreover, cytokines may play important roles in early-stage AD pathophysiology.

X-linked myotubular myopathy (XLMTM) is a rare genetic disorder caused by X-linked mutations in the MTM1 gene. Although heterozygous females are typically asymptomatic, affected cases have recently been reported. We herein report a case of XLMTM manifesting carrier of the pathogenic c.206dupG mutation in MTM1 with uncommon extramuscular symptoms. She developed gaze nystagmus and cognitive impairment in addition to muscle weakness. Electrophysiological studies and brain magnetic resonance imaging indicated the involvement of the central and peripheral nervous systems. XLMTM manifesting carriers may have a wider spectrum of clinical phenotypes than currently assumed. Appropriate follow-up of extramuscular and conventional muscular manifestations is important in such cases.