Pathological, imaging and genetic characteristics support the existence of distinct TDP-43 types in non-FTLD brains.

ABSTRACT: TDP-43 is present in a high proportion of aged brains that do not meet criteria for frontotemporal lobar degeneration (FTLD). We determined whether there are distinct TDP-43 types in non-FTLD brains. From a cohort of 553 brains (Braak neurofibrillary tangle (NFT) stage 0-VI), excluding cases meeting criteria for FTLD, we identified those that had screened positive for TDP-43. We reviewed 14 different brain regions in these TDP-43 positive cases and classified them into those with "typical" TDP-43 immunoreactive inclusions (TDP type-?), and those in which TDP-43 immunoreactivity was adjacent to/associated with NFTs in the same neuron (TDP type-?). We compared pathological, genetic (APOE4, TMEM106B and GRN variants), neuroimaging and clinical data between types, as well as compared neuroimaging between types and a group of TDP-43 negative cases (n?=?309). Two-hundred forty-one cases were classified as TDP type-? (n?=?131, 54%) or TDP type-? (n?=?110, 46%). Type-? cases were older than type-? at death (median 89 years vs. 87 years; p?=?0.02). Hippocampal sclerosis was present in 78 (60%) type-? cases and 16 (15%) type-? cases (p?

SUBMITTER: Josephs KA 

PROVIDER: S-EPMC6358471 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature