Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates

Brittany N Dugger1, Christopher M Clark, Geidy Serrano

  • 1From the Avid Radiopharmaceuticals (CMC, ML, APC, ADJ, MAM, MJP, DMS), Philadelphia, Pennsylvania; Banner Sun Health Research Institute (BND, GS, MM, MNS, LIS, TGB), Sun City, Arizona; Biospective Inc. and Montreal Neurological Institute (BJB, SPZ), McGill University, Montreal, Canada; Duke University Medical Center (REC, PMD), Durham, North Carolina; Banner Alzheimer's Institute (ASF, EMR), Phoenix, Arizona; Nova SE University (CHS), Ft Lauderdale, Florida; and Rush University Medical Center (JAS), Chicago, Illinois.

Insights

Amyloid PET imaging accurately reflects Alzheimer disease (AD) brain changes, even with other brain pathologies present. Florbetapir F-18 PET scans are reliable for measuring amyloid in AD patients, regardless of co-existing conditions like Lewy bodies.

Area of Science:

  • Neurology
  • Neuroimaging
  • Pathology

Background:

  • Alzheimer disease (AD) exhibits significant neuropathologic heterogeneity.
  • Concurrent pathologies can potentially affect in vivo amyloid imaging measures.

Purpose of the Study:

  • To assess if amyloid imaging measures in AD are influenced by co-existing pathologies.
  • To validate florbetapir F-18 (F-AV-45) PET imaging against postmortem histological β-amyloid quantification.

Main Methods:

  • Quantitative florbetapir F-18 PET imaging and postmortem neuropathologic examination were performed on 38 AD and 17 non-demented patients.
  • AD patients were subgrouped based on concurrent pathologies: Lewy bodies, white matter rarefaction, cerebral amyloid angiopathy, argyrophilic grains, and TAR DNA binding protein-43 inclusions.
  • Cortical to cerebellar amyloid imaging signal ratio (SUVr) and histological β-amyloid load were analyzed.

Main Results:

  • Strong correlations were found between SUVr and histological β-amyloid load across all AD subgroups (p < 0.001).
  • All AD subgroups showed significantly higher amyloid measures than non-demented patients.
  • AD cases with Lewy bodies had significantly lower SUVr compared to those without (p = 0.002); other pathologies did not yield significant differences.

Conclusions:

  • Florbetapir F-18 PET imaging is a reliable measure of amyloid burden in Alzheimer disease.
  • Amyloid PET imaging is not confounded by common neuropathologic heterogeneities found in AD patients.