In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia

Abstract

Objective: To investigate the specificity of in vivo amyloid imaging with [(11)C]-Pittsburgh Compound B (PIB) in Parkinson disease dementia (PDD).

Methods: We performed detailed neuropathologic examination for 3 individuals with PDD who had PIB PET imaging within 15 months of death.

Results: We observed elevated cortical uptake of [(11)C]-PIB on in vivo PET imaging in 2 of the 3 cases. At autopsy, all 3 individuals had abundant cortical Lewy bodies (Braak PD stage 6), and were classified as low-probability Alzheimer disease (AD) based on NIA-Reagan criteria. The 2 PIB-positive individuals had abundant diffuse Abeta plaques but only sparse neuritic plaques and intermediate neurofibrillary tangle pathology. The PIB-negative individual had rare diffuse plaques, no neuritic plaques, and low neurofibrillary tangle burden.

Conclusions: [(11)C]-Pittsburgh Compound B (PIB) PET is specific for fibrillar Abeta molecular pathology but not for pathologic diagnosis of comorbid Alzheimer disease in individuals with Parkinson disease dementia. The ability to specifically identify fibrillar Abeta amyloid in the setting of alpha-synucleinopathy makes [(11)C]-PIB PET a valuable tool for prospectively evaluating how the presence of Abeta amyloid influences the clinical course of dementia in patients with Lewy body disorders.

Figure 1 [¹¹C]-PIB PET images (A) Case 1. (B) Case 2. Increased signal is evident in multiple cortical areas in these 2 individuals, including orbitofrontal and prefrontal cortex, precuneus, and temporal lobes. (C) Case 3. (D) Control participant. These 2 individuals have minimal PIB signal in cortical areas. PIB retention in white matter areas is likely due to nonspecific binding (see text).

Figure 2 Postmortem examination, microscopic (case 2) (A) Aβ (10D5) immunohistochemistry. Low-power micrograph shows extensive Aβ deposits in the frontal lobe; there is also cerebral amyloid angiopathy in some leptomeningeal vessels. (B) Hematoxylin and eosin. In the substantia nigra, there is neuronal loss, extracellular pigment, gliosis, and a Lewy body (arrow) in a surviving pigmented neuron. (C–F) α-synuclein (LB-509) immunohistochemistry. (C) Lewy bodies and a Lewy neurite in the substantia nigra are more readily seen by α-synuclein immunohistochemistry. (D) Lewy bodies are present in the parahippocampal gyrus. (E) Lewy bodies are present in subfield CA4 of the hippocampus. (F) Dystrophic neurites are present in the CA1/CA2 subfields of the hippocampus. (G) Phosphorylated tau (PHF-1) immunohistochemistry. Neurofibrillary tangles and neuropil threads are present in the parahippocampal gyrus. (A, D–F bar = 500 μm; B, C, G, bar = 100 μm.)