Research ArticleAlzheimer’s Disease

Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease

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Science Translational Medicine  11 May 2016:
Vol. 8, Issue 338, pp. 338ra66
DOI: 10.1126/scitranslmed.aaf2362
  • Fig. 1. Mean tau and Aβ topographies.

    Mean PET tau and Aβ topographies in participants with and without clinical AD. Mean tau SUVR images averaged across participants with CDR0 (top row) or CDR>0 (bottom row). Images are presented in radiological convention. These images show relatively low pathology in cognitively normal individuals and increased pathology in the cognitively impaired group.

  • Fig. 2. PET tau and Aβ topographies are associated with disease severity.

    (A) Right singular vectors (V) of the SVD of the regional PET tau and Aβ data represented as topographies. The dimensionality of both tau and Aβ was estimated to be two. The first topography for both PET species broadly represents the mean (that is, all regions are homogeneously weighted). The second tau topography is present within the temporal lobe, and the second Aβ topography is largely seen in frontal and parietal lobes. Color bar represents regional weights within each singular component. (B) The representations of these topographies in individuals (left singular vectors, U) (that is, the original data projected onto these topographies) varied with CDR for both PET tau topographies and the second PET Aβ topography. Increasing disease severity (measured using the CDR) is associated with increasing representation of the present topographies in individuals. However, particularly in the Aβ data, there was significant heterogeneity. (C) Similar graphs as (B), but only participants with CSF analysis were included. Color in the CDR0 group indicates preclinical disease status: blue corresponds to healthy aging (that is, no Aβ or tau pathology), green corresponds to stage 1, and red corresponds to stage 2 of the CDR.

  • Fig. 3. Tau and Aβ in distinct topographies are strongly correlated.

    (A) Topographies for PET tau and PET Aβ imaging derived from canonical correlations that maximize the correlation between PET tau and Aβ deposition. (B) Scatter plot of the weights on each region demonstrates that PET tau and Aβ topographies are not significantly related. This is consistent with the typical topographies of tau and Aβ pathology being distinct. (C) The data projected onto the canonical variables revealed a robust positive relationship.

  • Fig. 4. CSF and neuropsychological performance are predicted by tau and Aβ topographies.

    Each row represents a single penalized regression model where either CSF protein or neuropsychological performance is predicted. ∑|βtau| and ∑|β| represent the total predictive weight of tau and Aβ topographies, respectively. Gray regions have no predictive weight. (A) Penalized regression models that predict CSF tau and Aβ42 using tau and Aβ topographies. Because CSF Aβ42 is inversely related to amyloid burden, negative weights indicate regions where topographies predict worse CSF Aβ42 pathology. (B) Penalized regression models that predict neuropsychological performance in each examined domain: global, episodic, semantic, and visuospatial (visuospat). Regions with negative values (displayed in cool colors) are where more PET pathology predicts lower cognitive performance.

  • Table 1. Cohort demographics.

    Demographics for the main cohort and two subsets. CSF, CSF assay; NP, neuropsychological testing; APOE, apolipoprotein ε.

    T807 + florbetapirT807 + florbetapir + CSFT807 + florbetapir + NP
    N463640
    Age (SD)75.4 (6.6)76.3 (6.6)75.7 (6.5)
    Male/female30/1625/1127/13
    CDR0/0.5/≥136/7/331/2/334/4/2
    APOE ε4+201618

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/8/338/338ra66/DC1

    Methods

    Fig. S1. PET tau and Aβ SUVR images from representative subjects in both the CDR0 and CDR>0 group.

    Table S1. Analysis of variance (ANOVA) results related to SVD topographies.

    Table S2. Mean PET and CSF correlation matrix.

    Table S3. Regional regression β values.

    Table S4. Comparison of PET tau SVD results.

    Table S5. Leave-one-out analysis results.

  • Supplementary Material for:

    Tau and Aβ imaging, CSF measures, and cognition in Alzheimer's disease

    Matthew R. Brier, Brian Gordon, Karl Friedrichsen, John McCarthy, Ari Stern, Jon Christensen, Christopher Owen, Patricia Aldea, Yi Su, Jason Hassenstab, Nigel J. Cairns, David M. Holtzman, Anne M. Fagan, John C. Morris, Tammie L. S. Benzinger, Beau M. Ances*

    *Corresponding author. Email: bances{at}wustl.edu

    Published 11 May 2016, Sci. Transl. Med. 8, 338ra66 (2016)
    DOI: 10.1126/scitranslmed.aaf2362

    This PDF file includes:

    • Methods
    • Fig. S1. PET tau and Aβ SUVR images from representative subjects in both the CDR0 and CDR>0 group.
    • Table S1. Analysis of variance (ANOVA) results related to SVD topographies.
    • Table S2. Mean PET and CSF correlation matrix.
    • Legend for table S3
    • Table S4. Comparison of PET tau SVD results.
    • Table S5. Leave-one-out analysis results.

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Table S3 (Microsoft Excel format). Regional regression β values.

    [Download Table S3]

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