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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Vydáno v:	Annals of neurology Ročník 85; číslo 2; s. 259 - 271
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken, USA John Wiley & Sons, Inc 01.02.2019 Wiley Subscription Services, Inc
Témata:	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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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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