Skip Navigation LinksHome > July 11, 2012 - Volume 23 - Issue 10 > Derlin-1-immunopositive inclusions in patients with Alzheime...
doi: 10.1097/WNR.0b013e3283552a75
Clinical Neuroscience and Neuropathology

Derlin-1-immunopositive inclusions in patients with Alzheimer’s disease

Honjo, Yasuyukia,b; Ito, Hidefumib; Horibe, Tomohisaa; Shimada, Hiroyukic; Nakanishi, Akid; Mori, Hiroshic; Takahashi, Ryosukeb; Kawakami, Kojia

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Amyloid plaques and neurofibrillary tangles are the major pathological hallmarks of Alzheimer’s disease. Neurofibrillary tangles are composed of filaments and paired helical filaments containing polymerized hyperphosphorylated tau protein. Derlin proteins are a family of proteins that are conserved in all eukaryotes, in which they function in endoplasmic reticulum-associated degradation. Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily and is believed to accelerate the folding of disulfide-bonded proteins in the luminal space of the endoplasmic reticulum. In this study, we found that derlin-1 and PDI were colocalized in neurofibrillary tangles in the brain of patients with Alzheimer’s disease. Derlin-1 and PDI may work as partners to avoid the accumulation of unfolded proteins in Alzheimer’s disease. Furthermore, we found that derlin-1 was immunopositive for neurofibrillary tangles and upregulated in Alzheimer’s disease and that derlin-1 may play an important role in endoplasmic reticulum-associated degradation during the pathogenesis of Alzheimer’s disease. We hypothesize that derlin-1 was upregulated to avoid the aggregation of unfolded proteins. Despite the upregulation of derlin-1, the functions of chaperone proteins and Alzheimer tau protein were lost and these proteins were also accumulated. Finally, they were involved in neurofibrillary tangles. These results suggest that derlin-1 may be associated with endoplasmic reticulum stress in neuronal cells in Alzheimer’s disease.

© 2012 Lippincott Williams & Wilkins, Inc.


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