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Cited by 217

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Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation

Kuusisto, E., Salminen, A., Alafuzoff, I.·2002·Neuropathology and Applied Neurobiology

Abstract

Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are two major histopathological lesions in Alzheimer's disease (AD). Although their aetiological relationship is unclear, both NFTs and dystrophic neurites of NPs display immunoreactivity for ubiquitin. This suggests that dysfunction in ubiquitin‐mediated proteolysis and the resulting accumulation of ubiquitin‐conjugated proteins may contribute to the origination of dystrophic neurites and NFTs. We recently discovered a novel constituent of neuropathological protein aggregates, ubiquitin‐binding protein p62, with evidence that the accumulation of ubiquitin‐conjugated proteins and p62 into cytoplasmic inclusions might be interconnected. In the present work we examined in detail the role of p62 in AD‐type pathology, i.e. NFTs, NPs and neuropil threads. Using immunohistochemistry for p62, ubiquitin and hyperphosphorylated tau, we analysed parietal cortical samples of 15 clinicopathologically verified AD cases and nine nondemented aged subjects with abundant NPs. We found that p62 immunoreactivity appears early during neurofibrillary pathogenesis and is invariably and stably present in NFTs. In contrast, p62 was absent or barely detectable in neuropil threads. Furthermore, NP‐associated dystrophic neurites were generally devoid of p62, regardless of their content of hyperphosphorylated tau and/or ubiquitin. The results suggest that early involvement of p62 might be critical in the aggregation of hyperphosphorylated tau into perikaryal aggregates, i.e. NFTs.

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Metadata

Authors
Kuusisto, E., Salminen, A., & Alafuzoff, I.
Venue
Neuropathology and Applied Neurobiology
Publisher
Wiley
Published
2002-06
Volume
28
Issue
3
Pages
228-237
ISSN
  • 0305-1846 (ISSN-L)
  • 1365-2990
OpenAlex
W2008735323
Cited by
217
References
7
FWCI
3.86
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation. https://app.cochat.ai/papers/10.1046/j.1365-2990.2002.00394.x
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Kuusisto, E., Salminen, A., & Alafuzoff, I. (2002). Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation. Neuropathology and Applied Neurobiology. https://doi.org/10.1046/j.1365-2990.2002.00394.x

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