BACKGROUND Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD. OBJECTIVE Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. METHODS We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. RESULTS The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ε4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOEε4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. CONCLUSION This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer's disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ε4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD.

Metagenomics is a primary tool for the description of microbial and viral communities. The sheer magnitude of the data generated in each metagenome makes identifying key differences in the function and taxonomy between communities difficult to elucidate. Here we discuss the application of seven different data mining and statistical analyses by comparing and contrasting the metabolic functions of 212 microbial metagenomes within and between 10 environments. Not all approaches are appropriate for all questions, and researchers should decide which approach addresses their questions. This work demonstrated the use of each approach: for example, random forests provided a robust and enlightening description of both the clustering of metagenomes and the metabolic processes that were important in separating microbial communities from different environments. All analyses identified that the presence of phage genes within the microbial community was a predictor of whether the microbial community was host-associated or free-living. Several analyses identified the subtle differences that occur with environments, such as those seen in different regions of the marine environment.

Klinefelter Syndrome is the most common sex chromosome aneuploidy in men and is characterized by the presence of an additional X chromosome (XXY). In some Klinefelter males, certain traits may be feminized or shifted from the male-typical pattern towards a more female-typical one. Among them might be partner choice, one of the most sexually dimorphic traits in the animal kingdom. We investigated the extent of feminization in XXY male mice (XXYM) in partner preference and gene expression in the bed nucleus of the stria terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy model. We tested for partner preference using a three-chambered apparatus in which the test mouse was free to choose between stimulus animals of either sex. We found that partner preference in XXYM was feminized. These differences were likely due to interactions of the additional X chromosome with the Y. We also discovered genes that differed in expression in XXYM vs. XYM. Some of these genes are feminized in their expression pattern. Lastly, we also identified genes that differed only between XXYM vs. XYM and not XXM vs. XYM. Genes that are both feminized and unique to XXYM vs. XYM represent strong candidates for dissecting the molecular pathways responsible for phenotypes present in KS/XXYM but not XXM. In sum, our results demonstrated that investigating behavioral and molecular feminization in XXY males can provide crucial information about the pathophysiology of Klinefelter Syndrome and may aid our understanding of sex differences in brain and behavior.

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