TY - JOUR
T1 - TDP-43 Neuropathologic Associations in the Nun Study and the Honolulu-Asia Aging Study
AU - Flanagan, Margaret E.
AU - Cholerton, Brenna
AU - Latimer, Caitlin S.
AU - Hemmy, Laura S.
AU - Edland, Steven D.
AU - Montine, Kathleen S.
AU - White, Lon R.
AU - Montine, Thomas J.
N1 - Funding Information:
This work was sponsored by grants from the NIH: UF1 AG053983, UF1 AG057707, P50 AG047366, P50AG05136, P50 NS062684, U01AG046871, U01 AG017155, and U01 AG019349.
Publisher Copyright:
© 2018 - IOS Press and the authors. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Transactive response binding protein-43 (TDP-43) cytoplasmic neuronal and glial aggregates (pathologic TDP-43) have been described in multiple brain diseases. We describe the associations between neuropathologically confirmed TDP-43 and cognition in two population-based cohorts: the Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS). In the HAAS, there was a significant association between hippocampal sclerosis (HS) and TDP-43 (OR = 11.04, p < 0.0001, 95% CI 3.57-34.13). In the NS, there were significant associations between TDP-43 and HS (OR=16.44, p>0.001 95%, CI 7.10-38.00) and Alzheimer's disease (AD) severity (OR=1.74, p=0.009, 95% CI 1.15-2.64). When cognitive scores were added to the model, HS remained significant but the other variables were not. When HS was removed from the model, the overall model remained significant and the associations between cognitive performance and TDP-43 (OR=2.11, p=0.022, 95% CI 1.11-4.02) were significant. In the NS, there was a significant association between cognitive performance and TDP-43 (OR 1.94 p=0.005, 95% CI 1.22-3.09) (HS remained significant, but AD did not). When HS was removed from the model, only CERAD was significant (OR=2.43 p<0.001, 95% CI 1.58-3.74). These results support a consistent association between pathologic TDP-43, HS, and the development of cognitive impairment in two large studies of brain aging, while the relationship between AD pathology and TDP-43 may vary according to cohort-specific features.
AB - Transactive response binding protein-43 (TDP-43) cytoplasmic neuronal and glial aggregates (pathologic TDP-43) have been described in multiple brain diseases. We describe the associations between neuropathologically confirmed TDP-43 and cognition in two population-based cohorts: the Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS). In the HAAS, there was a significant association between hippocampal sclerosis (HS) and TDP-43 (OR = 11.04, p < 0.0001, 95% CI 3.57-34.13). In the NS, there were significant associations between TDP-43 and HS (OR=16.44, p>0.001 95%, CI 7.10-38.00) and Alzheimer's disease (AD) severity (OR=1.74, p=0.009, 95% CI 1.15-2.64). When cognitive scores were added to the model, HS remained significant but the other variables were not. When HS was removed from the model, the overall model remained significant and the associations between cognitive performance and TDP-43 (OR=2.11, p=0.022, 95% CI 1.11-4.02) were significant. In the NS, there was a significant association between cognitive performance and TDP-43 (OR 1.94 p=0.005, 95% CI 1.22-3.09) (HS remained significant, but AD did not). When HS was removed from the model, only CERAD was significant (OR=2.43 p<0.001, 95% CI 1.58-3.74). These results support a consistent association between pathologic TDP-43, HS, and the development of cognitive impairment in two large studies of brain aging, while the relationship between AD pathology and TDP-43 may vary according to cohort-specific features.
KW - Alzheimer's disease
KW - TDP43
KW - associations
KW - hippocampal sclerosis
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U2 - 10.3233/JAD-180162
DO - 10.3233/JAD-180162
M3 - Article
C2 - 30452409
AN - SCOPUS:85058777494
SN - 1387-2877
VL - 66
SP - 1549
EP - 1558
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -
