Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer's Disease?

OBJECTIVES: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with "silent" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. METHODS: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. RESULTS: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate (r = .58, P = .002). CONCLUSION: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

Correlation between near-infrared Raman spectroscopy and the histopathological analysis of atherosclerosis in human coronary arteries.

BACKGROUND AND OBJECTIVES: Modern diagnostic methods such as near-infrared Raman spectroscopy (NIRS) allow quantification and evaluation of human atherosclerotic lesions, which can be useful in diagnosing coronary artery disease. The objective of the present study is to obtain feasible diagnostic information to detect atheromatous plaque using NIRS combined with discriminant analysis. STUDY DESIGN/MATERIAL AND METHODS: An 830 nm Ti: sapphire laser pumped by an argon laser provides near-infrared excitation. A spectrograph disperses light scattered from arterial tissue and a liquid-nitrogen cooled CCD detects the Raman spectra. A total of 111 arterial fragments were scanned and Raman results were compared with histopathology. Principal components analysis (PCA) and Mahalanobis distance (m-distance) were used to model an algorithm for tissue classification into three categories: non-atherosclerotic (NA), non-calcified (NC), and calcified (C) using Raman spectra. Spectra were randomly separated into training and prospective groups. RESULTS: It has been found that, for the NA tissue, the algorithm has sensitivity of 84 and 78% and specificity of 91 and 93% for training and prospective groups, respectively. For the NC tissue the algorithm has sensitivity of 88 and 90% and specificity of 88 and 83%. For the C tissue both sensitivity and specificity were maximum, 100%. CONCLUSIONS: An algorithm using PCA and discriminant analysis based on m-distance has been developed and successfully applied to diagnose coronary artery disease by NIRS obtaining good sensitivity and specificity for each tissue category.