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Objective: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions., Methods: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble α-syn, Aβ, and tau with recently developed sandwich ELISAs., Results: We detected a wide range of insoluble α-syn accumulation in LBD cases. The majority had substantial α-syn accumulation in most regions, and dementia severity correlated with neocortical α-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial Aβ accumulation, although the mean Aβ level in LBD was lower than in AD. The presence of Aβ was associated with greater α-syn accumulation. Tau accumulation accompanied Aβ in only one LBD case., Interpretation: LBD is associated with insoluble α-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between Aβ and α-syn accumulation suggests a pathophysiologic relationship between these two processes., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The contributors to persistent cognitive impairment and hippocampal atrophy in leucine-rich glioma-inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [ 18 F]flortaucipir PET neuroimaging associated with persistent cognitive impairment and hippocampal atrophy in four recovering LGI1 patients (3 men; median age, 67 [37-88] years). Imaging findings in cases were compared with those observed in age- and gender-similar cognitively normal individuals (n = 124) and individuals with early-symptomatic Alzheimer disease (n = 11). Elevated [ 18 F]flortaucipir retention was observed in the two LGI1 patients with hippocampal atrophy and persistent cognitive impairment, including one with autopsy-confirmed Alzheimer disease. Tau neuropathology may associate with cognitive complaints and hippocampal atrophy in recovering LGI1 patients., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Antemortem tau positron emission tomography imaging suggests elevated tau pathology in autosomal dominant versus late-onset Alzheimer's disease at equivalent clinical stages, but does not implicate the specific tau pathologies responsible. Here we made stereological measurements of tau neurofibrillary tangles, neuritic plaques, and neuropil threads and found compared to late-onset Alzheimer's disease, autosomal dominant Alzheimer's disease showed even greater tangle and thread burdens. Regional tau burden resembled that observed in tau imaging of a separate cohort at earlier clinical stages. Finally, our results suggest tau imaging measures total tau burden in Alzheimer's disease, composed predominantly of tangle and thread pathology., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: Increased translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), in glial cells of the brain has been used as a neuroinflammation marker in the early and middle stages of neurodegenerative diseases, such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB). In this study, we investigated the changes in TSPO density with respect to late stage AD and DLB., Methods: TSPO density was measured in multiple regions of postmortem human brains in 20 different cases: seven late stage AD cases (Braak amyloid average: C; Braak tangle average: VI; Aged 74-88, mean: 83 ± 5 years), five DLB cases (Braak amyloid average: C; Braak tangle average: V; Aged 79-91, mean: 84 ± 4 years), and eight age-matched normal control cases (3 males, 5 females: aged 77-92 years; mean: 87 ± 6 years). Measurements were taken by quantitative autoradiography using [ 3 H]PK11195 and [ 3 H]PBR28., Results: No significant changes were found in TSPO density of the frontal cortex, striatum, thalamus, or red nucleus of the AD and DLB brains. A significant reduction in TSPO density was found in the substantia nigra (SN) of the AD and DLB brains compared to that of age-matched healthy controls., Interpretation: This distinct pattern of TSPO density change in late stage AD and DLB cases may imply the occurrence of microglia dystrophy in late stage neurodegeneration. Furthermore, TSPO may not only be a microglia activation marker in early stage AD and DLB, but TSPO may also be used to monitor microglia dysfunction in the late stage of these diseases., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)