Neuropathology in Alzheimer's disease: awaking from a hundred-year-old dream.

Akihiko Nunomura*, Rudy J. Castellani, Hyoung Gon Lee, Paula I. Moreira, Xiongwei Zhu, George Perry, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


For one hundred years after Alois Alzheimer's first report of Alzheimer's disease (AD) in 1906, the pathological hallmarks of the disease, senile plaques and neurofibrillary tangles (NFTs), have been attractive targets for researchers. Therefore, not surprisingly, efforts to understand disease mechanisms have concentrated on the cell biology of amyloid-beta (Abeta) deposition as senile plaques or on the phosphorylation and aggregation of tau as NFTs. However, it now appears that this focus on pathology as a central contributor to disease may be misguided. Indeed, neurons associated with Abeta and NFTs in AD brain show a decrease in oxidative damage relative to those in vulnerable but morphologically intact areas of the brain, suggesting that neurodegenerative lesions are compensatory phenomena, and thus manifestations of cellular adaptation. That Abeta and tau accumulations indicate an age-related physiological reaction to chronic stress calls into question the rationale of current therapeutic efforts targeted toward lesion removal. Moreover, if this concept holds true for pathology in other neurodegenerative diseases, we may need to restructure our thinking and undergo a paradigm shift before substantial progress can be made in therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)pe10
JournalScience of aging knowledge environment : SAGE KE
Issue number8
StatePublished - May 3 2006
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Neuropathology in Alzheimer's disease: awaking from a hundred-year-old dream.'. Together they form a unique fingerprint.

Cite this