A Histochemical Analysis of Neurofibrillary Tangles in Olfactory Epithelium, a Study Based on an Autopsy Case of Juvenile Alzheimer's Disease

Abstract

The pathological changes of Alzheimer's disease (AD) begin 10-20 years before clinical onset, and it is therefore desirable to identify effective methods for early diagnosis. The nasal mucosa is a target tissue for measuring AD-related biomarkers because the olfactory nerve is the only cranial nerve that is exposed to the external environment. We describe an autopsy case of rapidly advanced juvenile AD (JAD), focusing on the olfactory system. The formation of senile plaques, neurofibrillary tangles (NFTs), and neuropil threads was examined in the temporal cortex, hippocampus, olfactory bulb, and olfactory and respiratory epithelia in the bilateral olfactory clefts. Neurodegenerative changes in the olfactory and respiratory epithelia and the pathological deposition of amyloid β42 (Aβ42) and phosphorylated tau were also examined. As a result, senile plaques, NFTs, and neuropil threads were found in the temporal cortex, hippocampus, and olfactory bulb. NFTs were also found in the olfactory epithelium. Degenerated olfactory cells and their axons stained positive for phosphorylated tau. Supporting cells in the degenerated olfactory epithelium stained positive for Aβ42. In conclusion, pathological biomarkers of AD were expressed in the degenerated olfactory epithelium of this JAD patient. This observation suggests that nasal samples may be useful for the diagnosis of AD.

Keywords: Alzheimer’s disease; amyloid β42; olfactory bulb; olfactory epithelium; phosphorylated tau.

Fig. 1.

Clinical course of the JAD patient in the present case (A). Cribriform plate and olfactory clefts (B and C). B: Frontal skull base (1) was cut around the cribriform plate (arrows) (2). Nasal tissue of the bilateral olfactory clefts was removed with the skull base (3). C: Bilateral olfactory clefts stained with HE. S, nasal septum; CP, cribriform plate; ST, superior turbinate. Bar = 1 mm. MMSE, Mini-Mental State Examination.

Fig. 2.

Microscopic images of the hippocampus (A–D), temporal cortex (E–H), olfactory bulb (I–L). A, E, and I, HE staining; B, F, and J, Aβ42 immunostaining; C, G, and K, phosphorylated tau (AT8) immunostaining; D, H, and L, GB silver staining. Aβ42-positive senile plaques (black arrows) were found in the hippocampus (B) and temporal cortex (F). NFTs (white arrows) and neuropil threads (white arrowheads) were also revealed in the hippocampus and temporal cortex by GB silver staining (D, H), and these threads stained positive for phosphorylated tau by immunohistochemistry (C, G). In the olfactory bulb, the glomerulus is the round structure in which synapses form between the olfactory nerve terminals and the dendrites of mitral, periglomerular, and tufted cells (I). Aβ42-positive senile plaques (black arrows) were found around the glomeruli (J). NFTs (white arrows) and neuropil threads (white arrowheads) exhibited positive phosphorylated tau and GB silver staining (K, L). Bar = 100 μm.

Fig. 3.

Representative microscopic images of the OE; typical OE (A, D, G, J), OE with fibrous changes (B, E, H, K), and OE with few olfactory cells (C, F, I, L). HE staining (A, B, C), amyloid β42 immunostaining (D, E, F), phosphorylated tau (AT8) immunostaining (G, H, I), and GB silver staining (J, K, L). Bar = 100 μm.

Fig. 4.

Microscopic images of OE with fibrous changes in the septum area of the olfactory clefts, immunostained for phosphorylated tau (AT8) (A). Some degenerated olfactory cells (black arrows) and their axons (white arrows) in the lamina propria of this epithelium stained positive for phosphorylated tau. Olfactory fascicles also stained partially positive for phosphorylated tau (white arrowheads) (D). Bar = 100 μm.