Olfactory dysfunction related to TDP-43 pathology in amyotrophic lateral sclerosis

To clarify a possible contribution of TDP-43 pathology to odor dysfunction in amyotrophic lateral sclerosis patients.An 83-year-old woman suffered from muscle weakness, which started to deteriorate during the previous half year. In addition to her pyramidal signs, lower motor involvement was shown by needle electromyography; this upper and lower motor neuron involvement was suggestive of probable ALS. She presented with severe odor impairments but relatively preserved cognitive functions. Her autopsy findings revealed TDP-43-positive inclusions in the spinal motor neurons and cerebral limbic system without significant tau or α-synuclein deposits.This case showed evidence suggesting that olfactory dysfunction was probably related to limbic TDP-43 pathology and was possibly independent of her Alzheimer pathology. Olfactory dysfunction does not necessarily indicate the presence of tau or α-synuclein pathology and could be an early sign of ALS with the limbic involvement of TDP-43 pathology even when cognitive functions are preserved.