Abstract
Background Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a TDP-43 proteinopathy, typically diagnosed in elderly patients. At present, a definitive diagnosis of LATE is made from neuropathological changes at autopsy. Neuropathological changes are characterised by the anatomical distribution of TDP-43 in the amygdala, hippocampus and middle frontal gyrus. Separately, LATE is most commonly associated with cognitive impairment, typically dementia of the Alzheimer’s type.
In terms of causation, TDP-43 is a protein encoded by the TARDBP gene. Of relevance to motor function, mutations involving the gene encoding TARDBP are causative for amyotrophic lateral sclerosis (ALS) in <5% of familial cases of ALS. Separately, TDP-43 protein is the hallmark ALS pathology, present at autopsy in >90% of patients diagnosed with ALS.
Cases The present case series describes two patients managed for ALS, who were subsequently diagnosed with LATE following post-mortem examination.
Case 1 (76M) initially presented with upper limb wasting and predominantly lower motor neurone pattern weakness, progressing to generalised disease with weakness over a 12 year period. Case 2 (79F) presented with disease-onset in the distal left upper limb, progressing to a left sided spastic hemiparesis and spastic dysarthria. She was diagnosed with PLS (likely Mills’ variant) and died 7 years after symptom onset.
Discussion Unifying phenotypic features of an ALS-presentation of LATE include limb-onset disease, slower disease progression compared to typical ALS, without prominent cognitive features. Recognition of LATE and its mimics is of increasing relevance, particularly in an ageing population, with potential interventions directed against TDP43.
