Loss of calbindin-D28K from aging human cholinergic basal forebrain: Relation to neuronal loss

Changiz Geula*, Jing Bu, Nicholas Nagykery, Leonard F M Scinto, Jennifer Chan, Jeffrey Joseph, Robert Parker, Chuang Kuo Wu

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Cholinergic neurons of the basal forebrain (BFCN) are selectively vulnerable in neurodegenerative disorders of the elderly, particularly in Alzheimer's disease (AD). We investigated age-related changes in the BFCN that may serve as a substrate for this vulnerability. We report a substantial and selective age-related loss of the calcium binding protein calbindin-D28K (CB) from the human BFCN. Unbiased stereological estimation indicated that, in individuals under age 65 years, 72% of the choline acetyltransferase (ChAT)-positive BFCN contained CB immunoreactivity. In individuals over age 65 years, only 28% of the BFCN contained CB immunoreactivity, a dramatic loss of 61%. Similar results were obtained using neuronal counts from matching single- or double-stained sections in a larger cohort. The loss of CB immunoreactivity was neurochemically specific. No age-related changes were observed in the number of CHAT- or low-affinity nerve growth factor receptor (p75NTR)- immunoreactive profiles. The loss of CB was greatest in very old individuals, in whom a small loss of BFCN was observed. Furthermore, the loss of CB displayed the same pattern as the loss of BFCN in AD and was more substantial in the posterior compared with the anterior BFCN sector, suggesting a role for CB in the selective vulnerability of BFCN in AD. The depletion of CB from the BFCN is likely to deprive these neurons of the capacity to buffer high levels of intracellular Ca2+ and thus to leave them vulnerable to pathological processes, such as those in neurodegenerative disorders, which can cause increased intracellular Ca2+, thus leading to their degeneration.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalJournal of Comparative Neurology
Volume455
Issue number2
DOIs
StatePublished - Jan 6 2003

Keywords

  • Alzheimer's disease
  • Calcium binding proteins
  • Choline acetyltransferase
  • Nerve growth factor receptor
  • Normal aging

ASJC Scopus subject areas

  • Neuroscience(all)

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    Geula, C., Bu, J., Nagykery, N., Scinto, L. F. M., Chan, J., Joseph, J., Parker, R., & Wu, C. K. (2003). Loss of calbindin-D28K from aging human cholinergic basal forebrain: Relation to neuronal loss. Journal of Comparative Neurology, 455(2), 249-259. https://doi.org/10.1002/cne.10475