Activity

Treatment of primary neurons with LRRK2 kinase inhibitors leads to prolonged kinase inhibition but does not alter tau pathology induction. The lack of an effect of LRRK2 kinase activity was further confirmed in primary neurons expressing LRRK2G2019S and with two different forms of pathogenic tau. In no case was there more than a minor change in tau pathology induction.

Together, our results indicate that LRRK2 kinase activity is not playing a major role in the induction of tau pathology in individual neurons. Understanding the impact of LRRK2 kinase inhibitors on pathology generation is important as kinase inhibitors move forward in clinical trials.

Together, our results indicate that LRRK2 kinase activity is not playing a major role in the induction of tau pathology in individual neurons. Understanding the impact of LRRK2 kinase inhibitors on pathology generation is important as kinase inhibitors move forward in clinical trials.

Early-onset Parkinson’s disease (EOPD), occurring between ages 40 and 55, carries social, societal, and personal consequences and may progress, with fewer comorbidities than typical, later-onset disease.

To examine the incidence and survival of EOPD and other Parkinsonism occurring before age 55 in the population-based cohort of residents in seven Minnesota counties.

A movement-disorder specialist reviewed all the medical records in a 2010-2015 Parkinsonism-incident cohort to confirm diagnosis and subtypes.

We identified 27 patients diagnosed at <  50 years with incident Parkinsonism 2010-1511 (41%) cases of EOPD, 13 (48%) drug-induced Parkinsonism, and 3 (11%) other Parkinsonism and 69 incident cases of Parkinsonism <  55 years of age. Overall incidence for Parkinsonism <  50 years was 1.98/100,000 person-years, and for EOPD was 0.81/100,000 person-years. In patients <  55 years, Parkinsonism incidence was 5.05/100,000 person-years in EOPD, 2.05/100,000 person-years. Levodopa-induced dyskinesia was present in 45%of EOPD (both <  50 years and <  55 years). Onset of cardinal motor symptoms was proximate to the diagnosis of EOPD, except for impaired postural reflexes, which occurred later in the course of EOPD. Among the 69 Parkinsonism cases <  55 years, 9 (13%; all male) were deceased (only 1 case of EOPD). Men had a higher mortality risk compared to women (p = 0.049).

The incidence of EOPD <  50 years was 0.81/100,000 person-years (1.98 in Parkinsonism all type); prior to 55 years was 2.05/100,000 person-years (5.05 in Parkinsonism all type) with higher incidence in men than women. Men with Parkinsonism, all type, had higher mortality compared to women.

The incidence of EOPD  less then  50 years was 0.81/100,000 person-years (1.98 in Parkinsonism all type); prior to 55 years was 2.05/100,000 person-years (5.05 in Parkinsonism all type) with higher incidence in men than women. Men with Parkinsonism, all type, had higher mortality compared to women.

Characterizing patients with Parkinson’s disease (PD) and cognitive impairment is important toward understanding their natural history.

Understand clinical, treatment, and cost characteristics of patients with PD pre- and post-cognitive impairment (memory loss/mild cognitive impairment/dementia or dementia treatment) recognition.

2,711 patients with PD newly diagnosed with cognitive impairment (index) were identified using administrative claims data. They were matched (11) on age and gender to patients with PD and no cognitive impairment (controls). These two cohorts were compared on patient characteristics, healthcare resource utilization, and total median costs for 3 years pre- and post-index using Chi-square tests, t-tests, and Wilcoxon rank-sum tests. Logistic regression was used to identify factors predicting cognitive impairment.

Comorbidity indices for patients with cognitive impairment increased during the 6-year study period, especially after the index. Enrollment in Medicare Advantage Prescrd post-identification. These data coupled with recommendations for annual screening for cognitive impairment in PD support the early diagnosis and management of cognitive impairment in order to optimize care for patients and their caregivers.

Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking.

The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project.

A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availabildence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.Granuloma formation is the pathologic hallmark of tuberculosis. Few studies have detailed the exact production of cytokines in human granulomatous inflammation and little is known about accessory molecule expressions in tuberculous (TB) granulomas. We aimed to identify some of the components of the immune response in granulomas in HIV-positive and -negative lymph nodes. We investigated the immunohistochemical profiles of CD4+, CD8+, CD68+, Th-17, Forkhead box (FOXP3) cells, accessory molecule expression (human leukocyte antigen [HLA] classes I and II), and selected cytokines (interleukins 2, 4, and 6 and interferon-γ) of various cells, in granulomas within lymph nodes from 10 HIV-negative (-) and 10 HIV-positive (+) cases. CD4+ lymphocyte numbers were retained in HIV- granulomas, whereas CD4+CD8 + cell were reversed in HIV+ TB granulomas. Akt inhibitor CD68 stained all histiocytes. Granulomas from the HIV+ group demonstrated a significant increase in FOXP3 cells. Interleukin-2 cytoplasmic expression was similar in both groups.