The long term objectives of this study are to evaluate the nature and specificity of the pathology that the investigators have discovered in the olfactory tissue of patients with Alzheimer's Disease (AD) and to understand the pathogenesis and relationship of the neuritic abnormalities to changes that occur in AD brain or in aging. This is the first demonstration of a peripheral site which shows pathological neuronal changes of AD. The investigators have demonstrated a highly significant association of these olfactory changes with AD, and these data strongly suggest that olfactory epithelial cells participate in the general abnormalities of AD. Olfactory receptor cells are neurons that lie in the nasal cavity and are accessible for study. They provide a """"""""window"""""""" to see what is happening in the brain and give us the opportunity to study the progression of disruptive processes from early to advanced stages, not only in AD, but also in other neurodegenerative diseases or in normal aging. A number of questions remain. The investigators have shown that olfactory tissue taken at autopsy from AD patients shows ectopic neurites that invade the epithelium and are immunoreactive for phosphorylated cytoskeletal proteins not normally found in olfactory epithelium. The investigators propose to extend the investigators study of autopsied patients to a larger group including AD as well as other neurodegenerative disease and aged non-demented patients to establish the specificity and prevalence of this phenomenon and to continue the biopsy studies of olfactory tissue that the investigators have begun on patients in early stages of AD. These biopsy studies will indicate if the pathological changes begin early and could provide the basis for examination of formative stages of the disease or development of diagnostic tests. Neither the distribution of the sensory areas in the nasal epithelium nor the extent of the pathology has been documented. These features will be mapped across the nasal epithelium on both sides of the nose with immunohistochemical techniques using newly-developed whole mount procedures. This will provide the information for accurate design of autopsy and biopsy studies and enable us to quantitate the amount of pathology. Furthermore, the identity and origin of the misdirected neurites in the epithelium is unknown. Characterization and identification of the neurites by use of additional antibodies will provide information for further understanding the pathologic phenomenology and its relationship to AD, and to identity molecular features that may discriminate neurites of AD from other pathologies. It may also give us insight into the basis for the abnormal neuritic outgrowth. Proteins of the cytoskeleton and those known to accumulate in plaques and neurofibrillary tangles will be studied, as will growth factors or other molecules suspected to participate in neurite extension. Olfactory receptor cell degenerate and are replaced from precursor cells throughout life, and this tissue could provide a source of cultured cells that express characteristics of neurodegenerative diseases for which no animal models are available.
| Feng, W H; Kauer, J S; Adelman, L et al. (1997) New structure, the ""olfactory pit,"" in human olfactory mucosa. J Comp Neurol 378:443-53 |
