title: Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer's disease.
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.
authors.affiliation: Laboratory for Cognitive and Molecular Morphometry, Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: David
authors.initials: D
authors.lastname: Riascos
authors.forename: Dianne
authors.initials: D
authors.lastname: de Leon
authors.forename: Alaina
authors.initials: A
authors.lastname: Baker-Nigh
authors.forename: Alexander
authors.initials: A
authors.lastname: Nicholas
authors.forename: Rustam
authors.initials: R
authors.lastname: Yukhananov
authors.forename: Jing
authors.initials: J
authors.lastname: Bu
authors.forename: Chuang-Kuo
authors.initials: CK
authors.lastname: Wu
authors.forename: Changiz
authors.initials: C
authors.lastname: Geula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D002118:Calcium