Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated

See Coulthard and Love (doi:10.1093/brain/awy153) for a scientific commentary on this article. The burden of co-pathologies across neurodegenerative diseases is unknown. Robinson et al. assess tau, Aβ, alpha-synuclein and TDP-43 proteinopathies in post-mortem individuals representing a spectrum of n...

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Veröffentlicht in:Brain (London, England : 1878) England : 1878), 2018-07, Vol.141 (7), p.2181-2193
Hauptverfasser: Robinson, John L, Lee, Edward B, Xie, Sharon X, Rennert, Lior, Suh, EunRan, Bredenberg, Colin, Caswell, Carrie, Van Deerlin, Vivianna M, Yan, Ning, Yousef, Ahmed, Hurtig, Howard I, Siderowf, Andrew, Grossman, Murray, McMillan, Corey T, Miller, Bruce, Duda, John E, Irwin, David J, Wolk, David, Elman, Lauren, McCluskey, Leo, Chen-Plotkin, Alice, Weintraub, Daniel, Arnold, Steven E, Brettschneider, Johannes, Lee, Virginia M.-Y, Trojanowski, John Q
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Zusammenfassung:See Coulthard and Love (doi:10.1093/brain/awy153) for a scientific commentary on this article. The burden of co-pathologies across neurodegenerative diseases is unknown. Robinson et al. assess tau, Aβ, alpha-synuclein and TDP-43 proteinopathies in post-mortem individuals representing a spectrum of neurodegenerative disease. Co-pathologies are common, with age and APOE ɛ4 status affecting co-pathology prevalence. The findings have implications for clinical trials focusing on monotherapies. Abstract Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-β, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72). Each group was divided into subgroups without or with co-pathologies. Age and sex matched logistic regression models compared co-pathology prevalence between groups. Co-pathology prevalence was similar between the minimal pathology group and most neurodegenerative diseases for each proteinopathy: tau was nearly universal (92-100%), amyloid-β common (20-57%); α-synuclein less common (4-16%); and TDP-43 the rarest (0-16%). In several neurodegenerative diseases, co-pathology increased: in Alzheimer's disease, α-synuclein (41-55%) and TDP-43 (33-40%) increased; in progressive supranuclear palsy, α-synuclein increased (22%); in corticobasal disease, TDP-43 increased (24%); and in neocortical Lewy body disease, amyloid-β (80%) and TDP-43 (22%) increased. Total co-pathology prevalence varied across groups (27-68%), and was increased in high Alzheimer's disease, progressive supranuclear palsy, and neocortical Lewy body disease (70-81%). Increased age at death was observed in the minimal pathology group, amyotrophic lateral sclerosis, and multiple system atrophy cases with co-pathologies. In amyotrophic lateral sclerosis and neocortical Lewy body disease, co-pathologies a
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awy146