Neuropathologic Heterogeneity Does Not Impair Florbetapir-Positron Emission Tomography Postmortem Correlates

Abstract

Neuropathologic heterogeneity is often present within Alzheimer’s disease (AD). We sought to determine if amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinicopathologically-defined AD and 17 non-demented cases (ND) with quantitative florbetapir F-18 (18F-AV-45) PET imaging during life and histological β-amyloid quantification and neuropathologic examination were assessed. AD cases were divided on the basis of concurrent pathologies, including those with Lewy bodies (N=21), white matter rarefaction (N=27), severe cerebral amyloid angiopathy (N=11), argyrophilic grains (N=5) and TDP-43 inclusions (N=18). Many cases exhibited more than one type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in six cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p values <0.001). All AD subgroups had significantly greater amyloid measures compared to ND, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with Lewy bodies had significantly decreased SUVr measures compared to AD cases without (p = 0.002); there were no other paired comparison differences. These findings indicate florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

Association of TDP-43 Pathology with Global and Regional 18F-Florbetapir PET Signal in the Alzheimer’s Disease Spectrum

“…We found no association of TDP-43 with global PVC SUVR values, consistent with a previous study [5], but could confirm our assumption that the presence of TDP-43 pathology would be associated with lower levels of hippocampal amyloid PET signal. One major contributor was the presence of hippocampal sclerosis that accounted for some of the TDP-43 effect; however, TDP-43 remained a relevant predictor even when accounting for hippocampal sclerosis.…”

Association of TDP-43 Pathology with Global and Regional 18F-Florbetapir PET Signal in the Alzheimer’s Disease Spectrum

“…We found no association of TDP-43 with global PVC SUVR values, consistent with a previous study [5], but could confirm our assumption that the presence of TDP-43 pathology would be associated with lower levels of hippocampal amyloid PET signal. One major contributor was the presence of hippocampal sclerosis that accounted for some of the TDP-43 effect; however, TDP-43 remained a relevant predictor even when accounting for hippocampal sclerosis.…”

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program

“…A recent publication is more indicative of the true incidence of these conditions in the BBDP population, as it is based on the conversion rates of BBDP subjects that were initially normal at their BBDP clinical assessments. 127 Also notable is the frequent co-existence of more than one major neuropathological condition in the same subject, 97,102,114,127,128 in agreement with such findings at other centers. 129…”

Amyloid Imaging: Poised for Integration into Medical Practice

“…The SUVR involves calculating the radioactivity of a specific region compared with another reference range. An interesting side note of this study was that patients with AD and Lewy bodies had significantly lower SUVRs compared with patients with AD without Lewy bodies [26]. This study demonstrates the ability of florbetapir PET scans to discriminate the presence of amyloid, despite the high clinical/pathologic variability of AD.…”

Association of TDP-43 Pathology with Global and Regional 18F-Florbetapir PET Signal in the Alzheimer’s Disease Spectrum

“…We found no association of TDP-43 with global PVC SUVR values, consistent with a previous study [5], but could confirm our assumption that the presence of TDP-43 pathology would be associated with lower levels of hippocampal amyloid PET signal. One major contributor was the presence of hippocampal sclerosis that accounted for some of the TDP-43 effect; however, TDP-43 remained a relevant predictor even when accounting for hippocampal sclerosis.…”

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program

“…A recent publication is more indicative of the true incidence of these conditions in the BBDP population, as it is based on the conversion rates of BBDP subjects that were initially normal at their BBDP clinical assessments. 127 Also notable is the frequent co-existence of more than one major neuropathological condition in the same subject, 97,102,114,127,128 in agreement with such findings at other centers. 129…”

Amyloid Imaging: Poised for Integration into Medical Practice

“…The SUVR involves calculating the radioactivity of a specific region compared with another reference range. An interesting side note of this study was that patients with AD and Lewy bodies had significantly lower SUVRs compared with patients with AD without Lewy bodies [26]. This study demonstrates the ability of florbetapir PET scans to discriminate the presence of amyloid, despite the high clinical/pathologic variability of AD.…”

Association of TDP-43 Pathology with Global and Regional 18F-Florbetapir PET Signal in the Alzheimer’s Disease Spectrum

“…We found no association of TDP-43 with global PVC SUVR values, consistent with a previous study [5], but could confirm our assumption that the presence of TDP-43 pathology would be associated with lower levels of hippocampal amyloid PET signal. One major contributor was the presence of hippocampal sclerosis that accounted for some of the TDP-43 effect; however, TDP-43 remained a relevant predictor even when accounting for hippocampal sclerosis.…”

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program

“…A recent publication is more indicative of the true incidence of these conditions in the BBDP population, as it is based on the conversion rates of BBDP subjects that were initially normal at their BBDP clinical assessments. 127 Also notable is the frequent co-existence of more than one major neuropathological condition in the same subject, 97,102,114,127,128 in agreement with such findings at other centers. 129…”

Amyloid Imaging: Poised for Integration into Medical Practice

“…The SUVR involves calculating the radioactivity of a specific region compared with another reference range. An interesting side note of this study was that patients with AD and Lewy bodies had significantly lower SUVRs compared with patients with AD without Lewy bodies [26]. This study demonstrates the ability of florbetapir PET scans to discriminate the presence of amyloid, despite the high clinical/pathologic variability of AD.…”