A closer look at LATE: a Case Report on a subtly evolving neurodegenerative disorder

Limbic-predominant age-related TDP-43 encephalopathy (LATE) often presents in older adults with a hippocampal-type amnestic syndrome that is clinically indistinguishable from Alzheimer's disease (AD). In the era of anti-amyloid therapies, misdiagnosis carries therapeutic consequences.

Single-patient case report. The patient provided written informed consent and all data included in this paper are de-identified.

A 71-year-old with isolated episodic memory impairment underwent neuropsychological testing, cerebrospinal fluid (CSF) AD biomarkers, and ¹⁸F-FDG PET in 2021. Baseline findings showed preserved global cognition, negative AD biomarkers, and mild bilateral medial temporal hypometabolism. Over the subsequent years, episodic memory declined, while daily function and other cognitive domains remained intact. MRI demonstrated bilateral medial temporal atrophy. Repeat CSF examination showed negative AD biomarkers, whereas NfL levels were markedly elevated. On repeat ¹⁸F-FDG PET, bilateral medial temporal hypometabolism progressed, while inferolateral temporal metabolism-usually reduced in AD-remained preserved.

The slowly progressing isolated amnestic profile, medial temporal-predominant neurodegeneration, high CSF NfL level, and persistently negative AD biomarkers supported the diagnosis of LATE. LATE should be actively considered in elderly patients with a hippocampal-type amnestic syndrome and negative AD biomarkers. This requires a high index of suspicion, but it is increasingly critical to avoid ineffective therapies and to refine clinical trial selection.