Acta Neuropathologica

, 122:565

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
Original Paper

DOI: 10.1007/s00401-011-0865-4

Cite this article as:
Riascos, D., de Leon, D., Baker-Nigh, A. et al. Acta Neuropathol (2011) 122: 565. doi:10.1007/s00401-011-0865-4

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-D28K. 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.

Keywords

Selective neuronal vulnerabilityAgingAlzheimer’s diseaseCalcium dysregulationCholinergic basal forebrain neuronsTangle pathology

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • David Riascos
    • 1
  • Dianne de Leon
    • 1
  • Alaina Baker-Nigh
    • 1
  • Alexander Nicholas
    • 2
  • Rustam Yukhananov
    • 3
  • Jing Bu
    • 2
    • 5
  • Chuang-Kuo Wu
    • 4
  • Changiz Geula
    • 1
  1. 1.Laboratory for Cognitive and Molecular Morphometry, Cognitive Neurology and Alzheimer’s Disease CenterNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of Medicine, Harvard Medical School and Division of GerontologyBeth Israel Deaconess Medical CenterBostonUSA
  3. 3.Precision BiosystemsMansfieldUSA
  4. 4.Department of NeurologyTexas Tech University HSC School of MedicineLubbockUSA
  5. 5.Berkshire Medical CenterPittsfieldUSA