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 journalArticlepeer-review

83 Scopus citations


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
Issue number5
StatePublished - Nov 2011


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

ASJC Scopus subject areas

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


Dive into the research topics of 'Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer's disease'. Together they form a unique fingerprint.

Cite this