Data are emerging to support the idea that mediators of angiogenesis are found in the Alzheimer's disease (AD) brain. The objective of this study is to compare the expression of the angiogenic mediators vascular endothelial growth factor (VEGF), angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD patients and age-matched controls.Our results indicate that angiopoietin-2 and VEGF are expressed by AD-but not control-derived microvessels. AD-derived microvessels also release higher levels of MMP-2 and MMP-9 compared to controls. The data show that despite high levels of MMP-9, assessed by western blot, MMP-9 activity is not detectable in AD microvessels. In this regard we find high levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not control vessels. Furthermore, we explore the ability of thrombin, previously shown to be present in AD microvessels, to affect TIMP expression in cultured brain endothelial cells and find that thrombin causes up regulation of TIMP-1. These data show that angiogenic changes occur in the microcirculation of the AD brain and suggest that if these changes are contributory to disease pathogenesis, targeting the abnormal brain endothelial cell would provide a novel therapeutic approach for the treatment of this disease.

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The schizophrenia prodrome has not been extensively studied in Africa. Identification of prodromal behavioral symptoms holds promise for early intervention and prevention of disorder onset. Our goal was to investigate schizophrenia risk traits in Kenyan adolescents and identify predictors of psychosis progression. 135 high-risk (HR) and 142 low-risk (LR) adolescents were identified from among secondary school students in Machakos, Kenya, using the structured interview of psychosis-risk syndromes (SIPS) and the Washington early recognition center affectivity and psychosis (WERCAP) screen. Clinical characteristics were compared across groups, and participants followed longitudinally over 0-, 4-, 7-, 14- and 20-months. Potential predictors of psychosis conversion and severity change were studied using multiple regression analyses. More psychiatric comorbidities and increased psychosocial stress were observed in HR compared to LR participants. HR participants also had worse attention and better abstraction. The psychosis conversion rate was 3.8%, with only disorganized communication severity at baseline predicting conversion (p=0.007). Decreasing psychotic symptom severity over the study period was observed in both HR and LR participants. ADHD, bipolar disorder, and major depression diagnoses, as well as poor occupational functioning and avolition were factors relating to lesser improvement in psychosis severity. Our results indicate that psychopathology and disability occur at relatively high rates in Kenyan HR adolescents. Few psychosis conversions may reflect an inadequate time to conversion, warranting longer follow-up studies to clarify risk predictors. Identifying disorganized communication and other risk factors could be useful for developing preventive strategies for HR youth in Kenya.

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