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

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.