Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

Alzheimer’s disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by systems biology approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework

Sex-specific cardiovascular comorbidities with associations in dermatologic and rheumatic disorders

Cardiology, dermatology, and rheumatology form a fascinating triad. Many skin and joint disorders are associated with cardiovascular comorbidities because they share etiologic elements. Female predominance is often remarkable and likely related to autoimmune pathology. Although studies have shown that X-encoded genes may be involved in the differences in immunity between males and females, other studies have also shown that sex chromosomes are irrelevant and that estrogens and androgens are responsible for the differences. The elevated immune activity in females provides a beneficial position in coping with a pathogenic stimulus but may also enhance their susceptibility to autoimmunity. The complexity of the immune system and its role as a defensive force against infection requires an armamentarium to precisely identify and selectively control inflammatory processes or cells which promote atherosclerosis. On the other hand, the inflammation in skin diseases seems to be an active source of diverse proinflammatory cytokines and chemokines which can predispose to cardiovascular comorbidities. Also, it has been shown that comorbidity disproportionately accelerates risk in women. The skin offers a readily available window to facilitate detection of risk factors or even to assist the diagnostic process regarding a variety of disorders, including those with cardiovascular involvement. Current imaging techniques provide exquisite capabilities for diagnosing and possibly even counteracting atherosclerotic plaque formation, before serious cardiovascular events occur. Combining imaging approaches (such as videocapillaroscopy, intravascular ultrasound, and FDG positron emission tomography) with insights based on immunology will likely accelerate advances in this area. We review major dermatologic manifestations and rheumatologic disorders which are associated with cardiac and vascular abnormalities. In particular we discuss sex-specific aspects concerning incidence and severity of cardiovascular disease associated with systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, atopic dermatitis, and hidradenitis suppurativa