Histological Markers in Nasal Mucosa of Patients with Alzheimer’s Disease

Abstract

Neuropathological changes such as dystrophic neurites and the presence of abnormal τ protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer’s disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of τ or β-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated. In these severe cases, τ immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and τ pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease.

Olfactory epithelium amyloid‐β and paired helical filament‐tau pathology in Alzheimer disease

“…Several early reports indicated frequent tau, amyloid, and ubiquitin immunoreactive neuritic pathologies in the OE biopsies of AD subjects,25, 26, 43 but subsequent studies did not support these 44, 45. Perry et al46 examined OE biospy sections from 8 subjects with probable AD and 3 controls and reported greater expression of oxidative damage markers in AD.…”

Smell identification test as an indicator for cognitive impairment in Alzheimer's disease

“…Therefore, a question arises about which level in olfactory processing explains the olfactory dysfunction observed in this study. The results of olfactory tests showing that disability in identifying smellsprecedes that in smell detection (Serby et al, 1991;Morgan et al, 1995) and neuropathologic findings suggesting the involvement of regions essential for olfactory processing (Hyman et al, 1984;Pearson et al, 1985;Hock et al, 1998) may imply a central origin of olfactory dysfunction rather than peripheral alteration in AD. Although our study did not examine odor detection threshold, we confirmed throughout the two olfactory tests that all subjects detected the presence of odorants administered, which implies that the deficit in odor identification was not due to an inability to detect smells, but rather may have been caused by an alteration in higher olfactory processing, although the trigeminal effect cannot be excluded in interpreting the results.…”

Olfaction deterioration in cognitive disorders in the elderly

“…These elements are also found throughout the olfactory nervous system in AD patients, justifying the early association between AD and olfactory loss [44]. Although some authors have found that even the OE in AD patients contains pathologically phosphorylated tau filaments [51], other authors have not been able to confirm this finding [52]. Tau-immunoreactive fibers have been found at the level of the OB where axons with pathological filaments from the OE enter [29].…”