Abstract
Abnormal neuronal accumulation and modification of TAR DNA binding protein 43 (TDP-43) have recently been discovered to be defining histopathological features of particular subtypes of frontotemporal dementia and amyotrophic lateral sclerosis, and are also common in aging, particularly coexisting with hippocampal sclerosis and Alzheimer's disease pathology. This case report describes a 72 year old Hispanic male with no family history of neurological disease, who presented at age 59 with obsessive behavior, anxiety, agitation, and dysphasia. Positron emission tomography imaging using the amyloid ligand 18F florbetapir (Amyvid) was positive. Postmortem examination revealed frequent diffuse and neuritic amyloid plaques throughout the cerebral cortex, thalamus, and striatum, Braak stage II neurofibrillary degeneration, and frequent frontal and temporal cortex TDP-43-positive neurites with rare nuclear inclusions. The case is unusual and instructive because of the co-existence of frequent cortical and diencephalic amyloid plaques with extensive TDP-43-positive histopathology in the setting of early-onset dementia and because it demonstrates that a positive cortical amyloid imaging signal in a subject with dementia does not necessarily establish that Alzheimer's disease is the sole cause.