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Frontotemporal lobar degeneration‐motor neuron disease (FTLD‐MND) with minimal brain pathology and novel atypical PKC inclusions: A case report
Author(s) -
Shao Charles Y.,
Sacktor Todd C.,
Zimmerman Earl,
Qian Jiang
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a21-d
Subject(s) - pathology , frontotemporal lobar degeneration , spinal cord , neuroscience , frontotemporal dementia , dentate gyrus , cerebellum , ataxia , atrophy , anterior horn cell , medicine , hippocampus , amyotrophic lateral sclerosis , dementia , psychology , disease
Search for pathologic substrates for neurodegenerative diseases continues to evolve. We previously showed that antibodies to atypical PKC (aPKC) isoforms: PKMζ and PKC ι/λ, labeled inclusions in both tauopathy and α‐synucleinopathy. Here we report aPKC aggregates in an unusual case of FTLD‐MND with ataxia. A man aged 52 presented with slurred speech, forgetfulness and inappropriate laughing, and rapidly developed ataxia, dysphagia, and myoclonus. Clinical examination: dementia, muscle fasciculations and Babinski signs. MRI: mild diffuse cerebral atrophy. He became wheelchair‐bound and expired in one year. Final clinical diagnosis was FTD with MND. Autopsy gross: atrophy of ventral spinal rootlets; mild frontotemporal atrophy. Microscopic: mild neuronal loss in cerebral cortex; the rest of cerebrum and cerebellum were unremarkable. There were no discernible inclusions. Spinal cord: marked neuronal loss, gliosis, bunina bodies, hyaline inclusions in anterior horn; and marked fiber loss in lateral and anterior columns. A few neurons were labeled with tau, ubiquitin, and neurofilament in neocortex, amygdala and hippocampus. Alpha‐synuclein was negative. Antibody to PKMζ labeled cytoplasmic aggregates in many neurons of dentate gyrus and cerebellar granular layer. The inclusions in spinal motoneurons were labeled with ubiquitin, neurofilament and PKC ι/λ. Molecular prion study ruled out CJD. While spinal cord changes are consistent with MND, changes in the brain are too minimal to explain dementia and ataxia. As PKMζ plays an important role in maintenance of excitatory synaptic strength, its aggregation in neurons of dentate gyrus and granular layer may lead to memory and balance impairments.