Microtubule reduction in Alzheimer's disease and aging is independent of τ filament formation

Adam D. Cash, Gjumrakch Aliev, Sandra L. Siedlak, Akihiko Nunomura, Hisashi Fujioka, Xiongwei Zhu, Arun K. Raina, Harry V. Vinters, Massimo Tabaton, Anne B. Johnson, Manuel Paula-Barbosa, Jesus Avíla, Paul K. Jones, Rudy J. Castellani, Mark A. Smith, George Perry*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

274 Scopus citations

Abstract

Biochemical studies show that phosphorylated τ, like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to the view that PHF formation leads to microtubule deficiency in Alzheimer's disease (AD). However, although this issue is one of the most important aspects to further understanding the cell biology of AD, no quantitative examination of microtubule diminution in AD and its relationship with PHFs has been performed. To examine this issue directly, we undertook a morphometric study of brain biopsy specimens from AD and control cases. Ultrastructural analysis of neurons was performed to compare the microtubule assembly state in neurons of diseased and control cases and to examine the effect of PHF accumulation. We found that both number and total length of microtubules were significantly and selectively reduced in pyramidal neurons from AD in comparison to control cases (P = 0.000004) but that this decrement in microtubule density was surprisingly unrelated to PHFs (P = 0.8). Further, we found a significant agedependent decrease in microtubule density with aging in the control cases (P = 0.016). These findings suggest that reduction in microtubule assembly is not dependent on 7 abnormalities of AD and aging.

Original languageEnglish (US)
Pages (from-to)1623-1627
Number of pages5
JournalAmerican Journal of Pathology
Volume162
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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