Transactive response DNA-binding protein 43 (TDP43) pathology was identified in 2006 as the primary protein abnormality in the rare diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). [1] However, according to recent findings, TDP43 pathology is common in old age, with approximately 50% of older persons showing evidence of the pathology at autopsy. [2] It has been demonstrated that TDP43 pathology in aging is strongly and independently associated with cognition, cognitive decline and increased risk of dementia above and beyond the contributions of other age-related neuropathologies. [2] TDP43 pathology in aging is mainly found in the medial temporal lobes with the being one of the first regions to be affected. [3] Therefore, the purpose of this project was to study associations of TDP43 in aging with amygdalar volume for the first time in a well-characterized large community cohort.Cerebral hemispheres were obtained from 202 deceased participants of the Rush Memory and Aging Project [4] and the Religious Orders Study [5], two longitudinal, epidemiologic clinical-pathologic cohort studies of aging. Demographic, clinical and neuropathologic information is included in the Table. All participants showed no evidence of FTLD. Hemispheres were imaged while immersed in 4% formaldehyde solution, using a 2D fast spin-echo sequence with multiple echo-times on a 3T clinical MRI scanner [6]. A multi-atlas approach was used to segment the amygdala from the ex-vivo brain MRI data, as described in a previous work [6]. Each volume measurement was normalized by the height of the participant. Following ex-vivo MRI, hemispheres underwent neuropathologic assessment by a board-certified neuropathologist blinded to all clinical and imaging findings. TDP-43 pathology was rated on 4 levels capturing the staging of the pathology: no inclusions; inclusions in amygdala only; inclusions in amygdala as well as entorhinal cortex or hippocampus CA1; and inclusions in amygdala, entorhinal cortex or hippocampus CA1, and neocortex [7]. Linear regression was used to investigate the link between amygdalar volume and TDP43 pathology, while controlling for AD pathology, Lewy bodies, hippocampal sclerosis, age at death, sex, education, postmortem interval to fixation and postmortem interval to imaging. Statistical significance was set at p<0.05. A significant negative correlation was detected between amygdalar volume and TDP43. Figure 1 shows an example of an ex-vivo MRI image.To our knowledge, this is the first study on morphometry and TDP43 in aging that utilizes a large community cohort [8]. Consequently, the present study provides information most representative of the relation between TDP43 pathology and amygdalar volume in the general population. The findings of this work offer support to literature on the effects of TDP43 pathology. This is an ongoing investigation with a growing number of participants.