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Background: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson disease but are believed to play no significant role in Lewy body disease (LBD)., Objectives: As the frequency of G2019S LRRK2 mutation is extremely high in North African patients with Parkinson disease, we postulate that the high prevalence of LBD in North Africa might be due to the same mutation because LBD and Parkinson disease share many clinical, pathological, and genetic features., Methods: We screened patients with LBD or prodromal LBD for the G2019S mutation of LRRK2., Results: A total of 162 patients were tested for the mutation, which was present in 5 of the 47 patients with North African ancestors. This is a much higher prevalence (10.6%) than in healthy North African subjects (1.45%) but lower than in North African patients with Parkinson disease (36% to 39%). Carriers tended to develop more often orthostatic hypotension and swallowing problems., Conclusions: Where previous studies in European and North American patients found no link between LRRK2 mutations and LBD, we found an LRRK2 mutation associated with Lewy body disease, namely the G2019S mutation that might be restricted to patients with North African ancestors. Our study illustrates the need to introduce ethnic diversity as stratifying factor in the analysis of genetic causes of neurodegenerative disorders. The current development of disease-modifying drugs modulating LRRK2 kinase activity could justify to screen North African patients with LBD for the G2019S LRRK2 mutation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Weight loss is a frequent complication of Alzheimer disease (AD), associated with increased morbidity and mortality. Increased appetite and weight gain are known side effects of the antidepressant mirtazapine. This analysis was undertaken to assess the safety and potential utility of mirtazapine to counteract weight loss in patients with AD or mixed AD (AD with cerebrovascular lesions). We performed a retrospective analysis of the clinical records of all outpatients attending our memory clinic for AD or mixed AD, who had received mirtazapine (30 mg daily) with the specific purpose of inducing weight or appetite gain. Data were available for a total of 22 patients (mean age, 80.9 y, 86.4% female). The mean weight at baseline was 52.4 kg and the mean BMI was 20.5 kg/m. 77.3% of the patients had gained weight after 3 months (mean gain, 1.93 kg or 3.9% of initial body weight) and 82.3% after 6 months (2.11 kg or 4.6%). One patient had to discontinue mirtazapine because of daytime sleepiness. Mirtazapine seems to be a safe and useful approach to counteract weight loss in AD, if possible in combination with nonpharmacological interventions. Body weight should be monitored during treatment to avoid excessive weight gain.

Background: Acute rejection of MHC class II-disparate bm12 skin grafts by C57BL/6 recipient mice is characterized by massive graft infiltration by eosinophils, together with increased intragraft amounts of IL-4 and IL-5 mRNA. IL-5 blockade prevents the intragraft eosinophil infiltration and prolongs the survival of skin allografts. As the differentiation of T cell precursors into Th2 cells is largely driven by IL-4, we investigated the role of IL-4 in MHC class II-disparate allograft rejection., Methods: We performed skin grafts from MHC class II incompatible bm12 mice into wild-type C57BL/6 mice (IL-4) or C57BL/6 IL-4 deficient mice (IL-4). Graft survival, in vitro T cell reactivity, and histology were compared., Results: We observed that 50% of IL-4 mice rapidly rejected their bm12 allograft, whereas the other 50% retained their graft 60 days after transplantation. Histological examination of bm12 allografts retained by IL-4 mice showed a normal appearance with no inflammatory infiltrate and no eosinophils. Among IL-4 mice that acutely rejected their bm12 skin graft, we observed a dense polymorphonuclear infiltrate. The depletion of neutrophils significantly prolonged bm12 graft survival., Conclusions: Eosinophil infiltrates, typical of MHC class II disparate acute skin graft rejection, are critically dependent on the availability of IL-4. IL-4 mice reject MHC class II disparate skin grafts by a pathway of rejection where neutrophils play a direct causal role.