Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) deposits, which come in myriad morphologies with varying clinical relevance. Previously, we observed an atypical Aβ deposit, referred to as the coarse-grained plaque. In this study, we evaluate the plaque’s association with clinical disease and perform in-depth immunohistochemical and morphological characterization. The coarse-grained plaque, a relatively large (Ø ≈ 80 µm) deposit, characterized as having multiple cores and Aβ-devoid pores, was prominent in the neocortex. The plaque was semi-quantitatively scored in the middle frontal gyrus of Aβ-positive cases (n = 74), including non-demented cases (n = 15), early-onset (EO)AD (n = 38), and late-onset (LO)AD cases (n = 21). The coarse-grained plaque was only observed in cases with clinical dementia and more frequently present in EOAD compared to LOAD. This plaque was associated with a homozygous APOE ε4 status and cerebral amyloid angiopathy (CAA). In-depth characterization was done by studying the coarse-grained plaque’s neuritic component (pTau, APP, PrPC), Aβ isoform composition (Aβ40, Aβ42, AβN3pE, pSer8Aβ), its neuroinflammatory component (C4b, CD68, MHC-II, GFAP), and its vascular attribution (laminin, collagen IV, norrin). The plaque was compared to the classic cored plaque, cotton wool plaque, and CAA. Similar to CAA but different from classic cored plaques, the coarse-grained plaque was predominantly composed of Aβ40. Furthermore, the coarse-grained plaque was distinctly associated with both intense neuroinflammation and vascular (capillary) pathology. Confocal laser scanning microscopy (CLSM) and 3D analysis revealed for most coarse-grained plaques a particular Aβ40 shell structure and a direct relation with vessels. Based on its morphological and biochemical characteristics, we conclude that the coarse-grained plaque is a divergent Aβ plaque-type associated with EOAD. Differences in Aβ processing and aggregation, neuroinflammatory response, and vascular clearance may presumably underlie the difference between coarse-grained plaques and other Aβ deposits. Disentangling specific Aβ deposits between AD subgroups may be important in the search for disease-mechanistic-based therapies.
Objective This meta‐analysis examines the efficacy of recently developed psychological treatments for anorexia nervosa, compared with control condition. Outcome criteria are weight gain, eating disorder pathology, and quality of life. Method Twelve thousand nine hundred ninety‐seven abstracts, published between 1980 and 2017, were retrieved. End‐of‐treatment data from 1,279 participants, from 15 of 17 eligible studies, were used to calculate pooled‐effect sizes (Hedges' g) for outcome using random‐effects model. Subgroup analyses were used to explore the influence of various patient and study characteristics. Results No significant differences between psychological treatment and controls were found on weight gain, g = 0.07, 95% CI [−0.09, 0.23], eating disorder pathology, g = 0.06, 95% CI [−0.10, 0.21], and quality of life, g = −0.11, 95% CI [−0.36, 0.15]. Studies including only patients over 18 years of age were more effective on weight gain than studies including adolescents as well. High‐quality studies and studies with reported therapist training had larger effects on weight gain and quality of life compared with low‐quality studies and studies without reported training. Conclusions Despite progress in the development of specialized treatments, the efficacy of psychological treatment over an active control condition could not be established. Outcomes, however, are obscured by low‐quality and heterogeneous studies.
It is shown for the first time that in acute respiratory distress syndrome, enhanced angiotensin-converting enzyme activity is paralleled by a reduced angiotensin-converting enzyme 2 activity, similar to that found in an experimental rat model of acute respiratory distress syndrome. The reduced angiotensin-converting enzyme 2 activity may be counteracted by restoring angiotensin-(1-7) level, thereby offering a novel treatment modality for this syndrome.
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