• Figure 4.
    Download figureOpen in new tabFigure 4. GluA4 levels are reduced in human postmortem AD brain.

    (A) Immunostaining of GluA4 demonstrates GluA4 is enriched on PV-IN in human cortex. Data were collected from four cases including occipital gyrus and parietal gyrus. (B and C) Representative western blot images (B) and quantification of GluA4 (C) in the frontopolar cortex (FPC), precuneus (PCU), middle frontal gyrus (MFG) and middle temporal gyrus (MTG) from controls and AD subjects. GluA4 is significantly down-regulated in PCU and MFG of AD individuals. FPC: control, n = 7; AD, n = 8. PCU: control, n = 15; AD, n = 19. MFG: control, n = 9; AD, n = 16. MTG: control, n = 10; AD, n = 18. *p<0.05 by two-tailed t test. Data represent mean ± SEM. (D) GluA4 levels correlate with NPTX2 in both control and AD group. Pearson correlation coefficient analysis was performed. (E and F) GluA4 expression did not correlate with NPTX2 in young adult brain. n = 10. Pearson correlation coefficient analysis was performed. (G and H) NPTX2 expression in young adult brain was higher than in aged controls. Young, n = 12; Aged, n = 15. **p<0.01 by two-tailed t test. Data represent mean ± SEM.

    DOI: http://dx.doi.org/10.7554/eLife.23798.014

    Figure 4—source data 1.Information of young healthy controls and aged healthy controls for brain analysis.

    DOI: http://dx.doi.org/10.7554/eLife.23798.015

    Download source data [figure-4—source-data-1.media-4.docx]
    Figure 6.
    Download figureOpen in new tabFigure 6. NPTX2 expression correlates with cognitive performance and measures of hippocampal volume.

    (A) NPTX2 expression in CSF correlates with cognitive function assayed by DRS in AD group. n = 30. p=0.0093 by Pearson correlation coefficient analysis. DRS: dementia rating scale. (B–D) No correlation was observed between CSF Aβ42 (B), tau (C) or p-tau181 (D) with DRS in AD group. n = 28. (E–H) NPTX2 expression in CSF correlates with cognitive function assayed by WCST test (E), semantic verbal fluency test (F), VRT test (G) and CVLT test (H). n = 20–28. WCST: Wisconsin Card Sorting Task; AFV: Semantic Verbal Fluency Test (‘Animals’, ‘Fruits’, ‘Vegetables’); VRT: Visual Reproduction Test; CVLT: California Verbal Learning Test. Pearson correlation coefficient analysis was performed. (I) Representative images of human brain MRI imaging. (J) NPTX2 levels in CSF correlate with hippocampal occupancy. n = 25 AD subjects. HOC: hippocampal occupancy.

    DOI: http://dx.doi.org/10.7554/eLife.23798.024

  • Table 1.

    Correlation analysis of CSF biomarkers with hippocampal size and clinical cognitive tests in AD subjects from second cohort.

    DOI: http://dx.doi.org/10.7554/eLife.23798.025

    Vs CSF NPTX2Vs CSF aβ42Vs CSF tauVs CSF p-Tau
    nPearson rp valuenPearson rp valuenPearson rp valuenPearson rp value
    Average Hippocampal Occupancy250.4830.015250.1890.36724−0.0830.701240.3600.084
    Dementia Rating Scale300.4670.009280.2250.24927−0.1370.497270.2960.134
    Digit Symbol Substitution240.4460.029230.1270.565220.0950.673220.0430.849
    Boston Naming Test280.2080.288270.0980.62826−0.0840.682260.2880.154
    Phonemic Verbal Fluency Test280.2000.30827−0.0790.69426−0.2070.310260.1330.519
    Semantic Verbal Fluency Test280.3850.043270.3960.041260.1210.557260.0360.863
    Wisconsin Card Sorting Task_categories achieved220.4450.038210.0460.84220−0.1790.45320−0.0570.812
    Wisconsin Card Sorting Task_perseverative errors22−0.3240.142210.1470.526200.0130.95620−0.1530.519
    Visual Reproduction Test_immediate recall240.4320.035230.1490.497220.3250.140220.2920.187
    Visual Reproduction Test_delayed recall240.3450.099230.1230.57722−0.3920.07222−0.0130.955
    Block Design280.4460.017270.0820.68326−0.1110.590260.0040.984
    Clock Drawing_command280.3370.079270.0400.84526−0.1190.563260.0870.673
    Clock
    Drawing_copy
    280.0110.955270.1060.60026−0.2460.225260.1610.434
    California Verbal Learning
    Test_list B recall
    200.5200.019200.6680.001190.2000.41119−0.1240.613
    California Verbal Learning Test_recognition200.1090.64720−0.0960.687190.0460.851190.2210.364
    • Significant correlations (p < 0.05) are highlighted in yellow.