Amyloid-A beta Peptide in Olfactory Mucosa and Mesenchymal Stromal Cells of Mild Cognitive Impairment and Alzheimer's Disease Patients

摘要

Patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) might develop olfactory dysfunction that correlates with progression of disease. Alteration of olfactory neuroepithelium associated with MCI may be useful as predictor of cognitive decline. Biomarkers with higher sensitivity and specificity would allow to understand the biological progression of the pathology in association with the clinical course of the disease. In this study, magnetic resonance images, apolipoprotein E (ApoE) load, Olfactory Connecticut test and Montreal Cognitive Assessment (MoCA) indices were obtained from noncognitive impaired (NCI), MCI and AD patients. We established a culture of patient-derived olfactory stromal cells from biopsies of olfactory mucosa (OM) to test whether biological properties of mesenchymal stromal cells (MSC) are concurrent with MCI and AD psychophysical pathology. We determined the expression of amyloid A peptides in the neuroepithelium of tissue sections from MCI and AD, as well as in cultured cells of OM. Reduced migration and proliferation of stromal (CD90(+)) cells in MCI and AD with respect to NCI patients was determined. A higher proportion of anosmic MCI and AD cases were concurrent with the ApoE epsilon 4 allele. In summary, dysmetabolism of amyloid was concurrent with migration and proliferation impairment of patient-derived stem cells.