Neuronal and nonneuronal quantitative BACE immunocytochemical expression in the entorhinohippocampal and frontal regions in Alzheimer's disease.
In this study, we quantitatively investigated the expression of beta-site amyloid precursor protein cleaving enzyme (BACE) in the entorhinohippocampal and frontal cortex of Alzheimer's disease (AD) and old control subjects. The semiquantitative estimation indicated that the intensity of BACE overall immunoreactivity did not differ significantly between AD and controls, but that a significantly stronger staining was observed in the hippocampal regions CA3-4 compared to other regions in both AD patients and controls. The quantitative estimation confirmed that the number of BACE-positive neuronal profiles was not significantly decreased in AD. However, some degeneration of BACE-positive profiles was attested by the colocalization of neurons expressing BACE and exhibiting neurofibrillary tangles (NFT), as well as by a decrease in the surface area of BACE-positive profiles. In addition, BACE immunocytochemical expression was observed in and around senile plaques (SP), as well as in reactive astrocytes. BACE-immunoreactive astrocytes were localized in the vicinity or close to the plaques and their number was significantly increased in AD entorhinal cortex. The higher amount of beta-amyloid SP and NFT in AD was not correlated with an increase in BACE immunoreactivity. Taken together, these data accent that AD progression does not require an increased neuronal BACE protein level, but suggest an active role of BACE in immunoreactive astrocytes. Moreover, the strong expression in controls and regions less vulnerable to AD puts forward the probable existence of alternate BACE functions.
Leuba
Geneviève
G
Center for Psychiatric Neuroscience and Service of Old Age Psychiatry, Department of Psychiatry-CHUV, University of Lausanne, CH-1008 Lausanne, Switzerland. Genevieve.Leuba@hospvd.ch
Wernli
Gwenaëlle
G
Vernay
André
A
Kraftsik
Rudolf
R
Mohajeri
M Hasan
MH
Saini
Krishan D
KD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000276:immunology* / Q000378:metabolism*; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques; D018728:Entorhinal Cortex / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged
D016564:Amyloid beta-Protein Precursor; D007074:Immunoglobulin G