%0 Journal Article
%T Association between transactive response DNA-binding protein of 43 kDa type and cognitive resilience to Alzheimer's disease: a case-control study.
%A Buciuc M
%A Whitwell JL
%A Tosakulwong N
%A Weigand SD
%A Murray ME
%A Boeve BF
%A Knopman DS
%A Parisi JE
%A Petersen RC
%A Dickson DW
%A Josephs KA
%J Neurobiol Aging
%V 92
%N 0
%D 08 2020
%M 32408057
%F 5.133
%R 10.1016/j.neurobiolaging.2020.04.001
%X Association between the transactive response DNA-binding protein of 43 kDa (TDP-43), its newly described types (type α/type β), and resilience to Alzheimer's disease neuropathological change (ADNC) defined as preservation of normal cognitive functioning despite advanced ADNC has been evaluated in this case-control study of 63 older adults. Twenty-one resilient to ADNC individuals were matched 1:2 to nonresilient (Alzheimer's dementia) using propensity scores, accounting for age at death, neuritic plaque density, and neurofibrillary tangle stage. Resilient and matched nonresilient participants were similar in terms of gender, apolipoprotein E ε4 carriership, education, occupation, AD, and other pathologies. Resilient participants had lower frequency of TDP-43 co-pathology compared to nonresilient (19% vs. 62%, p = 0.002). Among TDP-43-positive cases, TDP-43 type α inclusions were absent in resilient to ADNC participants and were dominant in matched nonresilient cases (65%, p = 0.03). TDP-43 and TDP-43 types appear to be one of the key pathological determinants of loss of cognitive resilience to ADNC and hence are important in the understanding of the clinical expression of ADNC.