Olfactory Dysfunction Correlates with Amyloid-Burden in an Alzheimer’s Disease Mouse Model

Emotional Brain Institute and Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 01/2010; 30(2):505-14. DOI: 10.1523/JNEUROSCI.4622-09.2010
Source: PubMed


Alzheimer's disease often results in impaired olfactory perceptual acuity-a potential biomarker of the disorder. However, the usefulness of olfactory screens to serve as informative indicators of Alzheimer's is precluded by a lack of knowledge regarding why the disease impacts olfaction. We addressed this question by assaying olfactory perception and amyloid-beta (Abeta) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-beta precursor protein. Such mice displayed progressive olfactory deficits that mimic those observed clinically-some evident at 3 months of age. Also, at 3 months of age, we observed nonfibrillar Abeta deposition within the olfactory bulb-earlier than deposition within any other brain region. There was also a correlation between olfactory deficits and the spatial-temporal pattern of Abeta deposition. Therefore, nonfibrillar, versus fibrillar, Abeta-related mechanisms likely contribute to early olfactory perceptual loss in Alzheimer's disease. Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects Abeta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Abeta.

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    • "A large body of data, including our own results, indicates that injury of the olfactory bulbs in rodents sets off many symptoms similar to major manifestations of AD (Bobkova et al. 2005; Doty 2009; Skelin et al. 2008). Importantly, it was shown using several transgenic animal models of AD that accumulation of amyloid-β starts in the glomerular layer of the olfactory bulbs (Wesson et al. 2010). The high level of survival in animals after bulbectomy as well as massive neuronal loss due to axon degeneration coupled with a sharp increase of amyloid precursor protein and Aβ (Struble et al. 1998; Bobkova et al. 2008; Kaminina et al. 2010) make OBX mice a model of choice to study TBItriggered neurodegeneration. "

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    • "Such changes are generally attributed to a deficit in odor detection (in the simple sniff or habituation test) or in discrimination (in the dishabituation test). However, in studies using more stringent methods quite different outcomes have been obtained: for example, studies on learning in neural cell adhesion molecules null mice (Gheusi et al. 2000; Schellinck et al. 2004); on the effects of intranasal zinc sulfate (Slotnick et al. 2007; Lim et al. 2009); on discrimination of enantiomers (Linster et al. 2001; McBride and Slotnick 2006); olfaction in Tg2576 strain mice (Wesson et al. 2010; Xu et al. 2014); and in within study comparisons of conditioning "
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    • "or 2 hours in Alexafluor 488 anti - mouse secondary antibody ( 1 : 500 ) . After incubation , tissue was rinsed a final time , mounted onto glass slides , dried and covered using GelMount . Staining groups always included sections from each age group and genotype . Histological quantification for thioflavin S and 6E10 was performed as described in Wesson et al . , 2010 . Quantification of Ab was performed with NIH ImageJ software . 4 brain areas , including OB , aPCX , HPX and lateral entorhinal cortex ( LEnt ) , were analyzed . Regions of interest ( ROIs ) were determined using standard anatomical coordinates [ 34 ] . Images were taken at 5x magnification and thioflavin S and anti - Ab florescence we"
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