Author:

Keywords:

SPG7, neurofibrillary tangles, tau, spastic paraplegia, ataxia, spastic ataxia, coiled bodies, Lewy bodies, paraplegin, Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Multidisciplinary, Chemistry, ALZHEIMERS-DISEASE, NEUROPATHOLOGIC ASSESSMENT, VESICLES, ATAXIA, BRAIN, GUAM, ATPases Associated with Diverse Cellular Activities, Aged, Basal Nucleus of Meynert, Cerebellar Nuclei, Gene Frequency, Gliosis, Humans, Intellectual Disability, Lewy Bodies, Male, Metalloendopeptidases, Muscle Spasticity, Neurites, Neurofibrillary Tangles, Neurons, Olivary Nucleus, Optic Atrophy, Spastic Paraplegia, Hereditary, Spinocerebellar Ataxias, Substantia Nigra, alpha-Synuclein, tau Proteins, 0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences, Chemical Physics, 3101 Biochemistry and cell biology, 3107 Microbiology, 3404 Medicinal and biomolecular chemistry

Abstract:

Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology.