Neuropathologic correlates of amyloid and dopamine transporter imaging in Lewy body disease

Abstract

ObjectiveTo develop imaging biomarkers of diseases in the Lewy body spectrum and to validate these markers against postmortem neuropathologic findings.MethodsFour cognitively normal participants with Parkinson disease (PD), 4 with PD with cognitive impairments, and 10 with dementia with Lewy bodies underwent amyloid imaging with [11C]Pittsburgh compound B (PiB) and dopamine transporter (DAT) imaging with [11C]Altropane. All 18 had annual neurologic examinations. All cognitively normal participants with PD developed cognitive impairment before death. Neuropathologic examinations assessed and scored Braak Lewy bodies, Thal distribution of amyloid, Consortium to Establish a Registry for Alzheimer's Disease neuritic amyloid plaques, Braak neurofibrillary tangles, and cerebral amyloid angiopathy, as well as total amyloid plaque burden in the superior frontal, superior parietal, occipital, and inferior temporal cortical regions. PET data were expressed as the standardized uptake value ratio with cerebellar reference. Analyses accounted for the interval between imaging and autopsy.ResultsAll 18 patients met neuropathologic criteria for Lewy body disease; the DAT concentration was low in each case. All patients with elevated [11C]PiB retention measured in a neocortical aggregate had β-amyloid deposits at autopsy. [11C]PiB retention significantly correlated with neuritic plaque burden and with total plaque burden. [11C]PiB retention also significantly correlated with the severity of both Braak stages of neurofibrillary tangle and Lewy body scores. Neuritic plaque burden was significantly associated with neurofibrillary tangle pathology.ConclusionAntemortem [11C]Altropane PET is a sensitive measure of substantia nigra degeneration. [11C]PiB scans accurately reflect cortical amyloid deposits seen at autopsy. These findings support the use of molecular imaging in the evaluation of patients with Lewy body diseases.

β-Amyloid PET and 123 I-FP-CIT SPECT in Mild Cognitive Impairment at Risk for Lewy Body Dementia

“… 36 Our finding of A+D+ frequency in MCI-LB (26.5%) is half the frequency from a recent report (55.6%) of 18 patients within the LB disease spectrum (Parkinson disease, DLB, and Parkinson disease dementia). 36 Whereas biomarker positivity appears to increase with increasing disease severity from MCI to dementia, patients with more core features did not have greater biomarker abnormalities. Thus, the number of core clinical features and imaging biomarkers were independent.…”

“…The relationship between amyloid-β and α-synuclein pathologies has been investigated in post-mortem and in vitro studies 33,34 , which suggested that amyloid-β and α-synuclein have the capacity to promote each other's aggregation 34,35 , and have synergistic Chen et al 14 toxicity in cells and transgenic mice 35,36 . However, the amyloid-β PET and 123 I-FP-CIT SPECT biomarker profile is relatively less documented in patients with DLB 37 . Our findings of A+D+ frequency in MCI-LB (26.5%) is half of the frequency from a recent report (55.6%) of 18 patients within the Lewy body disease spectrum (PD, DLB and PDD) 37 .…”

“…However, the amyloid-β PET and 123 I-FP-CIT SPECT biomarker profile is relatively less documented in patients with DLB 37 . Our findings of A+D+ frequency in MCI-LB (26.5%) is half of the frequency from a recent report (55.6%) of 18 patients within the Lewy body disease spectrum (PD, DLB and PDD) 37 . Whereas biomarker positivity appears to increase with increasing disease severity from MCI to dementia, patients with more core features did not have greater biomarker abnormalities.…”

Neuroimaging Advances in Parkinson's Disease and Atypical Parkinsonian Syndromes

“…Cerebral amyloid deposition can be assessed on PET using 11 C-PIB (Pittsburgh compound B) as well as using other 18 F-labeled radiotracers ( Table 2 ). Uptake on 11 C-PIB PET accurately reflects amyloid deposition antemortem as validated against postmortem neuropathologic findings ( 280 ). The apparent gradient of increasing amyloidopathy as visualized on PET can be conceptualized as PD < PD-MCI < PDD < DLB, which has been supported by pathology-proven investigations ( 281 , 282 ).…”

When does cerebral β‐amyloid deposition begin in Lewy body dementia?

“…A longitudinal follow-up study revealed that the majority of patients with DLB exhibited cerebral β-amyloid deposits/ plaques at the advanced stage of disease progression. [38][39][40][41] Many clinicopathological studies revealed that the load of cerebral β-amyloid deposition is significantly higher in DLB than PDD (Table 2). [6][7][8][9][10][11] These studies demonstrated that there was an association between a longer duration of parkinsonism prior to dementia and lower burden of β-amyloid deposition.…”