DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders

Neurobiology of Disease

David Mann¹  Tammaryn Lashley²  Tamas Revesz²  Ian Coulter³  David Williams³  Rina Bandopadhyay³  Andrew Lees³  Rohan de Silva³  Ravindran Kumaran³  Ann Kingsbury³ 

[1] Clinical Neurosciences Research Group, University of Manchester, Greater Manchester Neurosciences Centre, Hope Hospital, Salford, M6 8HD, UK;Department of Molecular Neuroscience and Queen Square Brain Bank, Institute of Neurology, Queen Square, WCIN 3BG, UK;Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, 1, Wakefield Street, WC1N 1PJ, UK;

关键词: DJ-1;    Tauopathies;    Hyperphosphorylated tau;    3R tau;    4R tau;   

DOI  :  

来源: DOAJ

【 摘 要 】

Mutations in the DJ-1 gene are associated with autosomal recessive Parkinson’s disease (PD), but its role in disease pathogenesis is unknown. This study examines DJ-1 immunoreactivity (DJ-1 IR) in a variety of neurodegenerative disorders, Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTLD) with Pick bodies, FTLD with MAPT mutations, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), in which hyperphosphorylated tau inclusions are the major pathological signature. DJ-1 IR was seen in a subset of neurofibrillary tangles (NFTs), neuropil threads (NTs), and neurites in extracellular plaques in AD; tau inclusions in AD contained both 3R and 4R tau. A subset of Pick bodies in FTLD showed DJ-1 IR. In PSP, DJ-1 IR was present in a few NFTs, NTs and glial cell inclusions. In CBD, DJ-1 IR was seen only in astrocytic plaques. In cases of FTLD with MAPT mutations that were 4R tau positive (i.e. N279K and exon 10+16 mutations), DJ-1 IR was present mostly in oligodendroglial coiled bodies. However, in MAPT R406W mutation cases, DJ-1 IR was associated mainly with NFTs and NTs and these were both 3R and 4R tau positive. No DJ-1 IR was present in FTLD with ubiquitin inclusions (FTLD-U). In AD and FTLD with Pick bodies, DJ-1 protein was enriched in the sarkosyl-insoluble fractions of frozen brain tissue containing insoluble hyperphosphorylated tau, thus strengthening the association of DJ-1 with tau pathology. Additionally using two-dimensional gel electrophoresis, we demonstrated accumulation of acidic pI isoforms of DJ-1 in AD brain, which may compromise its normal function. Our observations confirm previous findings that DJ-1 is present in a subpopulation of glial and neuronal tau inclusions in tau diseases and associated with both 3R and 4R tau isoforms.

【 授权许可】

Unknown