Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders

Objective To use digital histology in a large autopsy cohort of Lewy body disorder (LBD) patients with dementia to test the hypotheses that co‐occurring Alzheimer disease (AD) pathology impacts the anatomic distribution of α‐synuclein (SYN) pathology and that co‐occurring neocortical tau pathology i...

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Bibliographic Details
Published in:Annals of neurology Vol. 85; no. 2; pp. 259 - 271
Main Authors: Coughlin, David, Xie, Sharon X., Liang, Mendy, Williams, Andrew, Peterson, Claire, Weintraub, Daniel, McMillan, Corey T., Wolk, David A., Akhtar, Rizwan S., Hurtig, Howard I., Branch Coslett, H., Hamilton, Roy H., Siderowf, Andrew D., Duda, John E., Rascovsky, Katya, Lee, Edward B., Lee, Virginia M.‐Y., Grossman, Murray, Trojanowski, John Q., Irwin, David J.
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2019
Wiley Subscription Services, Inc
Subjects:
Aged
Aged, 80 and over
alpha-Synuclein - metabolism
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer Disease - psychology
Alzheimer's disease
Amyloid
Amyloid beta-Peptides - metabolism
Autopsies
Autopsy
Brain - metabolism
Brain - pathology
Cognitive ability
Cognitive tasks
Correlation analysis
Cortex (entorhinal)
Dementia
Dementia disorders
Entorhinal Cortex - metabolism
Entorhinal Cortex - pathology
Female
Heterogeneity
Histology
Histopathology
Humans
Lewy bodies
Lewy Body Disease - metabolism
Lewy Body Disease - pathology
Lewy Body Disease - psychology
Male
Mental Status and Dementia Tests
Movement disorders
Neocortex - metabolism
Neocortex - pathology
Neurodegenerative diseases
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson Disease - psychology
Parkinson's disease
Pathology
Patients
Plaque, Amyloid - pathology
Putamen
Putamen - metabolism
Putamen - pathology
Synuclein
Tau protein
tau Proteins - metabolism
Temporal cortex
Temporal lobe
ISSN:0364-5134, 1531-8249, 1531-8249
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Summary:Objective To use digital histology in a large autopsy cohort of Lewy body disorder (LBD) patients with dementia to test the hypotheses that co‐occurring Alzheimer disease (AD) pathology impacts the anatomic distribution of α‐synuclein (SYN) pathology and that co‐occurring neocortical tau pathology in LBDs associates with worse cognitive performance and occurs in a pattern differing from AD. Methods Fifty‐five autopsy‐confirmed LBD (Parkinson disease with dementia, n = 36; dementia with Lewy bodies, n = 19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD copathology (SYN + AD = 20) or little/no AD copathology (SYN−AD = 35). Digital measures of tau, β‐amyloid (Aβ), and SYN histopathology in neocortical and subcortical/limbic regions were compared between groups and related to antemortem cognitive testing. Results SYN burden was higher in SYN + AD than SYN−AD in each neocortical region (F1, 54 = 5.6–6.0, p < 0.02) but was equivalent in entorhinal cortex and putamen (F1, 43–49 = 0.7–1.7, p > 0.2). SYN + AD performed worse than SYN−AD on a temporal lobe–mediated naming task (t27 = 2.1, p = 0.04). Antemortem cognitive test scores inversely correlated with tau burden (r = −0.39 to −0.68, p < 0.05). AD had higher tau than SYN + AD in all regions (F1, 43 = 12.8–97.2, p < 0.001); however, SYN + AD had a greater proportion of tau in the temporal neocortex than AD (t41 = 2.0, p < 0.05), whereas AD had a greater proportion of tau in the frontal neocortex than SYN + AD (t41 = 3.3, p < 0.002). SYN + AD had similar severity and distribution of neocortical Aβ compared to AD (F1, 40–43 = 1.6–2.0, p > 0.1). Interpretation LBD patients with AD copathology harbor greater neocortical SYN pathology. Regional tau pathology relates to cognitive performance in LBD dementia, and its distribution may diverge from pure AD. Tau copathology contributes uniquely to the heterogeneity of cognitive impairment in LBD. Ann Neurol 2018; 1–13 ANN NEUROL 2019;85:259–271.
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DC, CM, DW, MG, JQT, DJI contributed to the conception and design of the study; DC, SX, ML, AW, CP, DAW, RSA, HH, HBC, RH, AS, JED, KR, EBL, VML, MG, JQT, DJI contributed to the acquisition and analysis of data; DC, DW, CM, DAW, RSA, AS, MG, JQT, DJI contributed to drafting a significant portion of the manuscript or figures.
Author Contributions
ISSN:0364-5134
1531-8249
1531-8249
DOI:10.1002/ana.25392