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Impact of morphologically distinct amyloid ß (Aß) deposits on 18F-florbetaben (FBB) PET scans

      Background

      Morphologically distinct Aß deposits, such as diffuse or neuritic Aß plaques (DIFF, NEUR), and vascular Aß (VASC) may be present in Alzheimer’s disease (AD). FBB has been validated as a biomarker of NEUR. It was the aim of this project to investigate the impact of the different forms of Aß deposits on FBB PET scans.

      Methods

      Brain tissue was collected from 87 end-of-life patients (64 AD patients) who underwent a FBB PET scan before death. Aß immunohistochemistry (IHC) was used for assessment of VASC. Aß IHC and Bielschowsky silver stain were used for assessment of NEUR and DIFF in frontal, occipital, anterior cingulate and posterior cingulate cortices. Cortical SUVRs were obtained in all ROIs using cerebellar grey matter as reference region. A linear regression model was fitted for each ROI as: SUVR=a0+an×n+ad×d+av×v, where a0, an, ad, av are constants, and n=NEUR, d=DIFF and v=VASC. n, d, and v were assigned two values: 0=Ab absent; 1=Ab present.

      Results

      In ROIs with high frequency of Aß (frontal, posterior cingulate), both DIFF (a=0.32 and 0.42) and NEUR (a=0.27 and 0.21) contributed significantly to the SUVR. In regions with low frequency of Aß (occipital, anterior cingulate), only DIFF contributed significantly to the SUVR (a=0.24 and 0.55). Presence of VASC contributed significantly to the SUVR only in the occipital region (a=0.13).

      Conclusions

      There was a significant impact of DIFF and VASC on FBB SUVR in brain regions characterized by low Ab load. These results underline the importance of measuring the topographic distribution of Ab aggregates and suggest the potential utility of FBB in detecting both DIFF and VASC Aß deposits.
      TableCoefficient values from the fitted models to each regional SUVR for each type of amyloid deposition (p values)
      Regionadiffuseaneuriticavascular
      Frontal0.32 (0.001)*0.27 (0.002)*0.09 (0.22)
      Posterior cingulate0.42 (<10-4)*0.21 (0.01)*-0.03 (0.77)
      Occipital0.24 (0.0001)*0.10 (0.07)0.13 (0.01)*
      Anterior cingulate0.55 (<10-4)*0.09 (0.37)-0.02 (0.85)
      * Statistically significant (p<0.05). Coefficient values>0 indicate contribution to SUVR