Passive Anti-Amyloid Beta Immunotherapies in Alzheimer's Disease: From Mechanisms to Therapeutic Impact.

Alzheimer's disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for Alzheimer's disease treatment by targeting the amyloid-beta peptide, a key pathological hallmark of the disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from the brain. This review offers an original and critical analysis of anti-amyloid immunotherapies by exploring several aspects. Firstly, the mechanisms of action of these therapies are reviewed, focusing on their ability to promote Aß degradation and enhance its efflux from the central nervous system. Subsequently, the extensive history of clinical trials involving anti-amyloid antibodies is presented, from initial efforts using first-generation molecules leading to mixed results to recent clinically approved drugs. Along with undeniable progress, the authors also highlight the pitfalls of this approach to offer a balanced perspective on this topic. Finally, based on its potential and limitations, the future directions of this promising therapeutic strategy for Alzheimer's disease are emphasized.

Autoimmune and Non-Autoimmune Comorbidities in Myasthenic Patients of East-European Descent: A Case-Control Study.

Background: As the life expectancy of patients with myasthenia gravis (MG) is improving, so the number of comorbidities continues to rise, with a potentially significant impact on the overall morbidity and mortality. The main aim of the study was to assess comorbidities of MG in a group of patients of East-European descent. Methods: We retrospectively compared 185 adult myasthenic patients with 895 sex- and age-matched controls, admitted from January 2013 to December 2021. Results: Of these patients, 60% had late-onset MG (LOMG), with a clear predominance of women in both the LOMG and early-onset (EOMG) types; and 23.8% of the patients had a radiological description consistent with thymoma. All myasthenic patients had at least one comorbidity; 20 (10.8%) of the patients associated at least one autoimmune comorbidity. Obesity (p < 0.01), type 2 diabetes (p < 0.0001), cerebrovascular diseases (p < 0.0001), essential hypertension (p < 0.01), and cardiac arrythmias (p < 0.0001) were more frequent in patients than in the control group. The granulocyte-to-lymphocyte ratio was higher in the myasthenic patients compared to the controls (p < 0.01 for LOMG). Discussion: We, thus, suggest a common chronic low-grade inflammatory background as a possible connection between MG subtypes and some of these apparently unconnected comorbidities. Conclusions: The East-European origin of the patients offered a different social and cultural angle of a disease studied mainly on populations of West-European and Asian descent.

Autoimmune myasthenia gravis and COVID-19. A case report-based review.

A potential relationship between COVID-19 infection and new onset myasthenia gravis (MG) has been suggested by the coexistence of these two diseases in a number of reports. This study aimed to assess their relationship by reviewing case studies of COVID-19 followed by new onset MG published between 01 December 2019 and 30 June 2023 identified by a search of PubMed/Medline database. In addition, we reviewed evidence in favour and against a potential cause and effect association, and described possible mechanisms that would underpin such a relationship. We identified 14 publications that reported 18 cases. Analysis showed the following features: age 19-83 years; 10 men/8 women; median time interval between COVID-19 and MG (17, 5-56 days); autoimmune comorbidities (4); generalised MG (14); ocular MG (4); thymoma (3); antiacetylcholine receptor antibody (16); antimuscle-specific kinase antibodies (2). All patients improved following treatment. Proof of direct causality between the two conditions can only be established in time by confirming epidemiological increase in the incidence of MG or elucidating pathogenic mechanisms to substantiate a possible cause-effect association, or both.

Autoimmune myasthenia gravis after COVID-19 in a triple vaccinated patient.

Despite a well characterized mechanism, myasthenia gravis (MG) remains a dilemma in terms of etiology. Several case reports and series of cases suggest a potential cause-effect relation between SARS-CoV-2 infection or vaccination and MG. We present the case of an autoimmune MG occurring post Covid-19 in an elderly male, vaccinated with three doses of the BNT162b2/Pfizer-BioNTech vaccine. The 78-year-old male was admitted in the Neurology Clinic in early November 2021 with double vision, bilateral ptosis, dysphonia and dysphagia, 16 days after receiving a third dose of the BNT162b2/Pfizer-BioNTech SARS-CoV-2 vaccine and 12 days after testing positive for SARS-CoV-2 infection. The symptoms began to emerge at 9 days after COVID-19 diagnosis. Clinical neurological examination included ice-pack test and intramuscular neostigmine, both with positive results. Myasthenia gravis positive diagnosis was confirmed by slow repetitive nerve stimulation and abnormally increased serum levels of antibodies against acetylcholine receptors. Due to patient's refusal of further hospitalization, he was discharged with therapy recommendations. Under treatment with oral pyridostigmine, but no oral corticosteroid due to therapeutic noncompliance, the patient was readmitted two months later with aggravated symptoms. The myasthenic crisis was successfully treated with intravenous immunoglobulins, corticosteroid therapy and oral pyridostigmine. The novelty of the current case resides in the fact that, to the best of our knowledge, appears to be the first case of MG clinically manifested after COVID-19 infection in a fully vaccinated patient.