Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer's disease

David Riascos, Dianne De Leon, Alaina Baker-Nigh, Alexander Nicholas, Rustam Yukhananov, Jing Bu, Chuang Kuo Wu, Changiz Geula*

*Corresponding author for this work

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The reasons for the selective vulnerability of distinct neuronal populations in neurodegenerative disorders are unknown. The cholinergic neurons of the basal forebrain are vulnerable to pathology and loss early in Alzheimer's disease and in a number of other neurodegenerative disorders of the elderly. In the primate, including man, these neurons are rich in the calcium buffer calbindin-D 28K. Here, we confirm that these neurons undergo a substantial loss of calbindin in the course of normal aging and report a further loss of calbindin in Alzheimer's disease both at the level of RNA and protein. Significantly, cholinergic neurons that had lost their calbindin in the course of normal aging were those that selectively degenerated in Alzheimer's disease. Furthermore, calbindin-containing neurons were virtually resistant to the process of tangle formation, a hallmark of the disease. We conclude that the loss of calcium buffering capacity in these neurons and the resultant pathological increase in intracellular calcium are permissive to tangle formation and degeneration.

Original languageEnglish (US)
Pages (from-to)565-576
Number of pages12
JournalActa Neuropathologica
Volume122
Issue number5
DOIs
StatePublished - Nov 1 2011

Keywords

  • Aging
  • Alzheimer's disease
  • Calcium dysregulation
  • Cholinergic basal forebrain neurons
  • Selective neuronal vulnerability
  • Tangle pathology

ASJC Scopus subject areas

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

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    Riascos, D., De Leon, D., Baker-Nigh, A., Nicholas, A., Yukhananov, R., Bu, J., Wu, C. K., & Geula, C. (2011). Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer's disease. Acta Neuropathologica, 122(5), 565-576. https://doi.org/10.1007/s00401-011-0865-4