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Additional file 4: Figure S3. CA analysis in a refined AD cohort illustrates a correlation with cognition and APOE status. A Scatter plot of CA/mm2 vs AD Neuropathology score, ranked 0–3 (0 = none, 1 = mild, 2 = moderate, 3 = severe) for 112 patients, 12 outliers excluded. Spearman r = -−0.2728, **p = 0.0046. B Plot of CA/mm2 of cognitively normal and demented patients at Braak Stages II, III, and IV. (112 patients, 12 outliers excluded). * p = 0.033 (Braak II), 0.021 (Braak III). C Plot of CA/mm2 in E3/E3 vs E3/E4 patients at Braak Stages I, II, III, IV, and V. (112 patients, 12 outliers excluded). *p = 0.0198. D Plot of CA/mm2 in E3/E3 vs E3/E4 and E4/E4 patients at Braak stages IV, V and VI. (112 patients, 12 outliers excluded). more...

Additional file 1: Figure S1. CA analysis of AD cases spanning Braak stages I–VI. A Representative brightfield images of full dentate gyrus architecture in patient tissue samples from Braak I–VI. Inset (dashed box) indicates sample region used in Fig. 2A. Scale bars = 900 µm (I, IV), 500 (III) 400 µm (V), 600 µm (II, VI). more...

Additional file 2: Figure S1. B CA/mm2 distribution plot for all 124 patients included in this study showing a skewed distribution of patient CA/mm2. C Logarithmic distribution plot of CA/mm2 for all 124 included in this study. D Box plot of CA/mm2 vs Braak Stage using all 124 patients included in this study. E Logarithmic box plot of CA/mm2 vs Braak Stage (I–VI) displaying all 124 patients included in this study. more...

Additional file 3: Figure S2. CA analysis of a refined AD cohort lacking outliers. Scatter plot of refined patient cohort, CA Density vs Braak Stage I, II, III, IV, V, and VI. (112 patients in black, 12 outliers identified by Grubb’s test, Q = 0.05, excluded patients in red). Statistically identified outliers are depicted in the table. Pathological and demographic information for outliers excluded from analysis, sorted by Braak stage. From left to right: Alzheimer’s neuropathological score, age, APOE allele, cognitive status, post-mortem interval, sex, dentate gyrus area, CA numerical count, and CA/mm2. more...

Additional file 5: Figure S4. The detection of human CA in CSF requires primary IgM antibodies. A Shown is a secondary only control stain for immunofluorescent detection of CA in human patient CSF. No CA are detected in the absence of primary IgM antibody, though we note the detection of some non-specific debris. AlexaFluor anti-Ms IgG1 (red) and Anti-Ms IgM (green, brightness increased for visualization). Scale bar = 100 µm. Bottom row frames are insets from top row frames within the dashed white compartment. more...

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P more...