The cholinergic deficit coincides with Aβ deposition at the earliest histopathologic stages of Alzheimer disease

Thomas G. Beach, Yu Min Kuo, Katharyn Spiegel, Mark R. Emmerling, Lucia I. Sue, Katrina Kokjohn, Alex E. Roher

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Aβ concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two- tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque- free cases. In the inferior temporal gyms, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Aβ concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.

Original languageEnglish
Pages (from-to)308-313
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Issue number4
DOIs
Publication statusPublished - 2000 Apr

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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