Pathologic Accumulation of α-Synuclein and Aβ in Parkinson Disease Patients With Dementia

Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

“…This finding has not been previously reported, but it is consistent with prior evidence that cortical LBD is associated with higher amyloid burden, but not higher Braak stage (Obi et al, 2008), and that demented individuals with mixed neuropathologies typically have lower levels of ADNC compared to individuals with ADNC only (Nagy et al, 1997; Postupna et al, 2015). Discrepancies in prior findings regarding LBD and neurofibrillary tangles, in which some studies found positive associations (Iseki et al., 2003; Jellinger and Attems, 2008; Sonnen et al, 2010) while others did not (Chung et al, 2015; Kotzbauer et al, 2012; Obi et al, 2008; Schneider et al., 2012) may be accounted for by the non-monotonic association we observed between cortical LBD and level of ADNC. Interactions between amyloid and α-synuclein may lead to an alternative pathologic and clinical presentation than ADNC only, in which neurofibrillary tangles are more predominant (Jellinger and Attems, 2008; Swirski et al, 2014; Wirths et al, 2000).…”

Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

“…This finding has not been previously reported, but it is consistent with prior evidence that cortical LBD is associated with higher amyloid burden, but not higher Braak stage (Obi et al, 2008), and that demented individuals with mixed neuropathologies typically have lower levels of ADNC compared to individuals with ADNC only (Nagy et al, 1997; Postupna et al, 2015). Discrepancies in prior findings regarding LBD and neurofibrillary tangles, in which some studies found positive associations (Iseki et al., 2003; Jellinger and Attems, 2008; Sonnen et al, 2010) while others did not (Chung et al, 2015; Kotzbauer et al, 2012; Obi et al, 2008; Schneider et al., 2012) may be accounted for by the non-monotonic association we observed between cortical LBD and level of ADNC. Interactions between amyloid and α-synuclein may lead to an alternative pathologic and clinical presentation than ADNC only, in which neurofibrillary tangles are more predominant (Jellinger and Attems, 2008; Swirski et al, 2014; Wirths et al, 2000).…”

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in L ewy Body Dementias

“…Equally, other studies have suggested that AD pathology in particular plays a role in cognitive decline in Lewy body dementias (11,20,23,36). In agreement with previous data (28), the present study illustrates that it is not uncommon to observe α-synuclein, senile Αβ plaque and phosphotau pathology in all three dementias. Studies have previously attempted to relate the cognitive decline in PDD and DLB to the presence of AD pathology with conflicting results, the latter probably arising as a consequence of issues relating to diagnosis and sample population (29).…”

PET Imaging in Movement Disorders

“…Also, 17 out of the 21 patients with Lewy body disease had a low amyloid burden (distribution volume ratio <1.15) but 4 of these 17 patients had elevated AV uptake in spite of a low amyloid burden. This was in stark contrast to our prior pathologic findings 107 . The nascent data with AV PET needs to be interpreted with caution given the important lesson from our experience with PiB that further validation especially pathologic correlation could be the key missing piece; also binding specificity of the AV tracer in an environment with PD pathology may be different from AD.…”

Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

“…This finding has not been previously reported, but it is consistent with prior evidence that cortical LBD is associated with higher amyloid burden, but not higher Braak stage (Obi et al, 2008), and that demented individuals with mixed neuropathologies typically have lower levels of ADNC compared to individuals with ADNC only (Nagy et al, 1997; Postupna et al, 2015). Discrepancies in prior findings regarding LBD and neurofibrillary tangles, in which some studies found positive associations (Iseki et al., 2003; Jellinger and Attems, 2008; Sonnen et al, 2010) while others did not (Chung et al, 2015; Kotzbauer et al, 2012; Obi et al, 2008; Schneider et al., 2012) may be accounted for by the non-monotonic association we observed between cortical LBD and level of ADNC. Interactions between amyloid and α-synuclein may lead to an alternative pathologic and clinical presentation than ADNC only, in which neurofibrillary tangles are more predominant (Jellinger and Attems, 2008; Swirski et al, 2014; Wirths et al, 2000).…”

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in L ewy Body Dementias

“…Equally, other studies have suggested that AD pathology in particular plays a role in cognitive decline in Lewy body dementias (11,20,23,36). In agreement with previous data (28), the present study illustrates that it is not uncommon to observe α-synuclein, senile Αβ plaque and phosphotau pathology in all three dementias. Studies have previously attempted to relate the cognitive decline in PDD and DLB to the presence of AD pathology with conflicting results, the latter probably arising as a consequence of issues relating to diagnosis and sample population (29).…”

PET Imaging in Movement Disorders

“…Also, 17 out of the 21 patients with Lewy body disease had a low amyloid burden (distribution volume ratio <1.15) but 4 of these 17 patients had elevated AV uptake in spite of a low amyloid burden. This was in stark contrast to our prior pathologic findings 107 . The nascent data with AV PET needs to be interpreted with caution given the important lesson from our experience with PiB that further validation especially pathologic correlation could be the key missing piece; also binding specificity of the AV tracer in an environment with PD pathology may be different from AD.…”

Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

“…This finding has not been previously reported, but it is consistent with prior evidence that cortical LBD is associated with higher amyloid burden, but not higher Braak stage (Obi et al, 2008), and that demented individuals with mixed neuropathologies typically have lower levels of ADNC compared to individuals with ADNC only (Nagy et al, 1997; Postupna et al, 2015). Discrepancies in prior findings regarding LBD and neurofibrillary tangles, in which some studies found positive associations (Iseki et al., 2003; Jellinger and Attems, 2008; Sonnen et al, 2010) while others did not (Chung et al, 2015; Kotzbauer et al, 2012; Obi et al, 2008; Schneider et al., 2012) may be accounted for by the non-monotonic association we observed between cortical LBD and level of ADNC. Interactions between amyloid and α-synuclein may lead to an alternative pathologic and clinical presentation than ADNC only, in which neurofibrillary tangles are more predominant (Jellinger and Attems, 2008; Swirski et al, 2014; Wirths et al, 2000).…”

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in L ewy Body Dementias

“…Equally, other studies have suggested that AD pathology in particular plays a role in cognitive decline in Lewy body dementias (11,20,23,36). In agreement with previous data (28), the present study illustrates that it is not uncommon to observe α-synuclein, senile Αβ plaque and phosphotau pathology in all three dementias. Studies have previously attempted to relate the cognitive decline in PDD and DLB to the presence of AD pathology with conflicting results, the latter probably arising as a consequence of issues relating to diagnosis and sample population (29).…”

PET Imaging in Movement Disorders

“…Also, 17 out of the 21 patients with Lewy body disease had a low amyloid burden (distribution volume ratio <1.15) but 4 of these 17 patients had elevated AV uptake in spite of a low amyloid burden. This was in stark contrast to our prior pathologic findings 107 . The nascent data with AV PET needs to be interpreted with caution given the important lesson from our experience with PiB that further validation especially pathologic correlation could be the key missing piece; also binding specificity of the AV tracer in an environment with PD pathology may be different from AD.…”