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[P2–443]: SUBJECTIVE MEMORY COMPLAINTS AND COGNITIVE DECLINE
Author(s) -
Slachevsky Andrea,
Parrao Teresa,
Lillo Patricia,
Forno Gonzalo,
Villagra Roque,
Thumala Daniela,
Amieva Helene,
Zitko Pedro,
Galvez Rodrigo,
Assar Rodrigo,
Wenk Elisabeth
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1099
Subject(s) - psychosocial , neuropsychology , psychology , complaint , cognition , cognitive decline , association (psychology) , population , clinical psychology , medicine , gerontology , psychiatry , dementia , disease , psychotherapist , environmental health , political science , law
Background:Olfactory pathway and in particular bulb and the olfactory tract are invariably involved in most of neurodegenerative disorders showing the deposition of the specific disease associated proteins such as beta-amyloid, tau, alpha-synuclein, TDP-43 and prion protein (PrP). In patients with prion disease, we set up a diagnostic test for prion detection using nasal brushing. This procedure allows a gentle collection of olfactory neurons (ON) from a wide surface area of olfactory epithelium without damaging the olfactory function since ONs undergo to an ongoing replacing. Methods:We carried out an immunohistochemistry, molecular and biochemical study on olfactory brushings obtained from 40 healthy subjects. Each subject underwent to nasal brushing and collected cells were processed for immunostaining and biochemical analyses. Expression of beta-amyloid, tau and phospho-tau, alpha-synuclein, TDP-43 and PrP in mature and immature neurons were characterized by double immunostaining using neuronal markers such as anti-Neun, Tuj-1, antiNestin and anti-olfactory marker protein (OMP). Post-translational modifications of the neurodegeneration associated proteins were determined by immunoblot analysis. Results: OM samplings were characterized by a rich neuronal population at different stage of maturation. OMP positive cells showed the typical morphology of ciliated neurons in contrast to globoid conformation of immature neurons. OMP positive cells were positive to beta-amyloid, tau and phospho-tau, alpha-synuclein, TDP-43 and PrP but with a different cell distribution. In addition ubiquitin positive inclusions were observed. In contrast, OMP negative cells resulted negative to all proteins associated to neurodegeneration. Western blot analysis of OMP positive cells, enriched by cell sorter, confirmed quantitatively the morphological results and in particular that alfa-synuclein is partially phosphorylated. Conclusions: This study shows for the first time in humans that mature ONs express beta-amyloid, tau and phospho-tau, alpha-synuclein, TDP-43 and PrP and this expression is closely related with neuronal maturation. In particular, this expression seems to start when ONs become mature. We also showed that in normal subjects, these proteins undergo to abnormal post-translational modifications, such as phosphorylation and ubiquitination, which lead to protein aggregation with toxic effects on cell metabolism. These evidences might explain why the olfactory system is early involved in neurodegenerative process.