Assessing limbic-predominant age-related TDP-43 encephalopathy (LATE) in the Sydney Brain Bank
Adele Lusson, Andrew Affleck, Heather McCann, Glenda Halliday and Claire Shepherd
Neuroscience Research Australia, Sydney, New South Wales, Australia
University of New South Wales, Sydney, New South Wales, Australia
Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia
Abnormal aggregates of TDP-43 protein seen in limbic regions of aged individuals is common and has been associated with cognitive impairment. This limbic-predominant age-related TDP-43 encephalopathy (LATE) has recently been suggested to account for a large proportion of non-Alzheimer's disease cognitive decline, especially in individuals of advanced age (>80 years). We examined the frequency of LATE in donors who were either asymptomatic or had a dominant dementia diagnosis over the age of 80 years in the Sydney Brain Bank (N=137). Our data demonstrate 33% of asymptomatic and 38% of dementia cases over the age of 80 years met criteria for LATE. LATE neuropathology commonly associated with Alzheimer's disease neuropathological change regardless of cognitive status (31% of asymptomatic cases versus 43% of dementia cases) but also showed a common association with cerebrovascular neuropathology (30% of asymptomatic and 43% of dementia cases). Only 1% of dementia cases had pure LATE neuropathology compared to 5% of asymptomatic cases, although the number of pure LATE cases was low in both cohorts (<2). LATE cases were significantly older than non-LATE cases (83 vs. 79 years on average, p=0.015). In general, our work supports LATE as a neuropathological entity that is seen more commonly with advanced age. However, we observe LATE neuropathological change in a third of individuals over the age of 80 years in the absence of cognitive decline.