Abstract
Alzheimer's disease is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest reported signs of Alzheimer's disease is olfactory dysfunction, which may manifest in a variety of ways. The present study sought to address this issue by investigating odor coding in the anterior piriform cortex, the primary cortical region involved in higher order olfactory function, and how it relates to performance on olfactory behavioral tasks. An olfactory habituation task was performed on cohorts of transgenic and age-matched wild-type mice at 3, 6 and 12 months of age. These animals were then anesthetized and acute, single-unit electrophysiology was performed in the anterior piriform cortex. In addition, in a separate group of animals, a longitudinal odor discrimination task was conducted from 3–12 months of age. Results showed that while odor habituation was impaired at all ages, Tg2576 performed comparably to age-matched wild-type mice on the olfactory discrimination task. The behavioral data mirrored intact anterior piriform cortex single-unit odor responses and receptive fields in Tg2576, which were comparable to wild-type at all age groups. The present results suggest that odor processing in the olfactory cortex and basic odor discrimination is especially robust in the face of amyloid β precursor protein (AβPP) over-expression and advancing amyloid β (Aβ) pathology. Odor identification deficits known to emerge early in Alzheimer's disease progression, therefore, may reflect impairments in linking the odor percept to associated labels in cortical regions upstream of the primary olfactory pathway, rather than in the basic odor processing itself.
Highlights
In early stages of Alzheimer’s disease (AD) and mild cognitive impairment, olfactory dysfunction has been shown to precede other cognitive impairments
The present results suggest that in the face of advancing pathology created by amyloid b, odor coding and olfactory perceptual acuity remain surprisingly robust in an animal model of AD
These data support recent behavioral observation in other animal models of amyloid b precursor protein (AbPP) over-expression [42,43], and for the first time demonstrate that the spared odor discrimination behavior reflects intact anterior PCX (aPCX) single-unit odor coding
Summary
In early stages of Alzheimer’s disease (AD) and mild cognitive impairment, olfactory dysfunction has been shown to precede other cognitive impairments. Olfactory dysfunction can manifest as deficits in the detection and discrimination of odors, though in the earliest stages of AD it is most commonly expressed as an odor identification impairment [1,2,3]. Changes typically seen in AD such as amyloid b (Ab) accumulation and tau tangles are often detected in structures involved in olfaction such as olfactory bulb (OB) and entorhinal cortex before spreading to other areas [4,5,6,7,8]. The effect of AD pathologies such as Ab deposition and plaque formation and phosphorylated tau aggregation on the different olfactory processing relays in the cortex is still poorly understood. Without sufficient knowledge of how AD pathology affects the encoding and transmission of olfactory information, it is difficult to construct a complete picture of how early dysfunction in this system predicts later cognitive decline
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