The Link Between Frontotemporal Dementia and Autoimmunity: A Case Presentation and Literature Review.

Dementia disorders are an important public health issue and thus of particular clinical importance. Frontotemporal dementia, although less prevalent than Alzheimer's disease, presents in a significant number of cases in younger populations. Yet, it is a comparatively rare disease process, with a low yearly incidence. Frontotemporal dementia remains an exciting and ever-evolving area of research with most recent studies investigating the role of inflammation in the degeneration pathognomonic of the disease. Here, we describe a case that highlights the connection between inflammation and neurodegeneration. Specifically, we examine a patient with long-standing rheumatoid arthritis and antiphospholipid syndrome who developed frontotemporal dementia, potentially as a result of the chronic inflammatory state.

Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast.

Acetaldehyde, a primary metabolite of alcohol, forms DNA adducts and disrupts the DNA replication process, causing genomic instability, a hallmark of cancer. Indeed, chronic alcohol consumption accounts for approximately 3.6% of all cancers worldwide. However, how the adducts are prevented and repaired after acetaldehyde exposure is not well understood. In this report, we used the fission yeast Schizosaccharomyces pombe as a model organism to comprehensively understand the genetic controls of DNA damage avoidance in response to acetaldehyde. We demonstrate that Atd1 functions as a major acetaldehyde detoxification enzyme that prevents accumulation of Rad52-DNA repair foci, while Atd2 and Atd3 have minor roles in acetaldehyde detoxification. We found that acetaldehyde causes DNA damage at the replication fork and activates the cell cycle checkpoint to coordinate cell cycle arrest with DNA repair. Our investigation suggests that acetaldehyde-mediated DNA adducts include interstrand-crosslinks and DNA-protein crosslinks. We also demonstrate that acetaldehyde activates multiple DNA repair pathways. Nucleotide excision repair and homologous recombination, which are both epistatically linked to the Fanconi anemia pathway, have major roles in acetaldehyde tolerance, while base excision repair and translesion synthesis also contribute to the prevention of acetaldehyde-dependent genomic instability. We also show the involvement of Wss1-related metalloproteases, Wss1 and Wss2, in acetaldehyde tolerance. These results indicate that acetaldehyde causes cellular stresses that require cells to coordinate multiple cellular processes in order to prevent genomic instability. Considering that acetaldehyde is a human carcinogen, our genetic studies serve as a guiding investigation into the mechanisms of acetaldehyde-dependent genomic instability and carcinogenesis.