Abstract 7- 1130-1145
Category: Clinical
At the end of the session, participants will be able to:
- To recognize brain histological changes in the oldest-old
- To become aware of brain resilience in the oldest-old
- To explore possible relationships between TDP-43 and astrocytosis
COI Disclosure:
None to disclose.
Presenter
David Munoz is a neuropathologist.
Authors
David G. Munoz1,2,4 & Julia Keith3,4
1 Division of Pathology, Unity Health, Toronto, ON, Canada 2 Keenan Research Centre for Biomedical Research, The Li Ka Shing Knowledge Institute, St.Michael’s Hospital, Toronto, ON, Canada, 3Division of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada
Target Audience:
CanMEDS:
Medical Expert (the integrating role), Communicator, Health Advocate, Scholar
A 108 Year Old Brain With Near Normal Cognition
A 108 year old male veteran lived in a nursing home, and participated in regular cognitive testing. Despite being legally blind and hearing impaired, his last MMSE, 3 years prior to death at age 105 was 25/30. The brain weighed 1365 gr and showed severe bilateral hippocampal atrophy. H&E sections showed complete neuronal loss of CA1 bilaterally, and severe loss of vermal Purkinje cell, but the neuronal populations of the neocortex and entorhinal cortex were mostly preserved. Reactive gliosis was prominent throughout the cingulate cortex, mostly restricted to grey-white junction in the frontal, parietal and temporal cortices, and absent in the occipital cortex. The main protein deposit was TDP-43, present in the frontotemporal neocortex as neuronal cytoplasmic inclusions and thick short process in the superficial layers (type A), and in the hippocampus as a dense network of thin process in CA1. Tau labeled neurofibrillary tangles in the entorhinal cortex and the locus ceruleus, and plaque-like structures in the absence of amyloid in the hippocampus. Beta amyloid plaques were moderately dense in the neocortex, and accompanied by vascular deposits in the occipital cortex only. Alpha-synuclein Lewy bodies were present in the locus ceruleus, but not the substantia nigra. The surprising findings were the extent of hippocampal lesions compatible with near normal function, and the severe cortical astrocytosis out of proportion to abnormal protein deposits or neuronal loss. We propose that astrocytosis may develop in response to neuronal TDP-43, made conspicuous by ageing, and play a neuroprotective role, as postulated in ALS.