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Locally reduced levels of acidic FGF lead to decreased expression of 28‐kDa calbindin and contribute to the selective vulnerability of the neurons in the entorhinal cortex in Alzheimer's disease
Author(s) -
Thorns Veronika,
Licastro Federico,
Masliah Eliezer
Publication year - 2001
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1046/j.1440-1789.2001.00399.x
Subject(s) - calbindin , neuroprotection , entorhinal cortex , biology , neuroscience , microbiology and biotechnology , medicine , hippocampus , endocrinology , immunohistochemistry , immunology
Recent studies demonstrate that a disturbed calcium‐homeostasis leading to increased susceptibility to excitotoxic triggers plays a major role in the neurodegenerative process initiating in layer 2 of the entorhinal cortex (EC2) during Alzheimer's disease (AD). Thus, proteins binding free Ca 11 (i.e. calbindin) and factors regulating these proteins are of great importance for the neuroprotective–neurotoxic balance in the affected brain regions. In the present combined human and in vitro study evidence is provided that altered levels of the acidic fibroblast growth factor (aFGF) and calbindin expression are concomitantly present in EC2 neurons and have interactive effects. A dramatic loss of aFGF‐ and calbindin‐labeled EC2 neurons was found. Further analysis of the surviving EC2 neurons revealed a strong immunoreactivity to calbindin and aFGF. In vitro experiments show that aFGF regulates calbindin expression, because treatment of differentiating neurons with recombinant aFGF increases calbindin expression in a time‐dependent fashion. The data imply that a reduced expression of aFGF in EC2 neurons of AD brains leads to lower levels of calbindin resulting in decreased neuroprotective capacity.