Early Olfactory Involvement in Alzheimer’s Disease

University Institute of Pathology, Division of Neuropathology, 1011, CHUV, Lausanne, Switzerland.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques (Impact Factor: 1.53). 02/2003; 30(1):20-5. DOI: 10.1017/S0317167100002389
Source: PubMed


In Alzheimer's disease (AD) the olfactory system, including the olfactory bulb, a limbic paleocortex is severely damaged. The occurrence of early olfactory deficits and the presence of senile plaques and neurofibrillary tangles in olfactory bulb were reported previously by a few authors. The goal of the present study was to analyze the occurrence of AD-type degenerative changes in the peripheral part of the olfactory system and to answer the question whether the frequency and severity of changes in the olfactory bulb and tract are associated with those of the cerebral cortex in AD.
In 110 autopsy cases several cortical areas and the olfactory bulb and tract were analyzed using histo- and immunohistochemical techniques. Based on a semiquantitative analysis of cortical senile plaques, neurofibrillary tangles and curly fibers, the 110 cases were divided into four groups: 19 cases with severe (definite AD), 14 cases with moderate, 58 cases with discrete and 19 control cases without AD-type cortical changes.
The number of cases with olfactory involvement was very high, more than 84% in the three groups with cortical AD-type lesions. Degenerative olfactory changes were present in all 19 definite AD cases, and in two of the 19 controls. The statistical analysis showed a significant association between the peripheral olfactory and cortical degenerative changes with respect to their frequency and severity (P < 0.001). Neurofibrillary tangles and neuropil threads appear in the olfactory system as early as in entorhinal cortex.
The results indicate a close relationship between the olfactory and cortical degenerative changes and indicate that the involvement of the olfactory bulb and tract is one of the earliest events in the degenerative process of the central nervous system in AD.

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Available from: Judith Miklossy, Oct 29, 2014
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    • "Accumulations of neuropil threads (NPTs) and NFTs have been found in the OBs of patients diagnosed with definite AD, many patients diagnosed with probable AD or MCI, and some cognitively normal older adults [36]. In addition , the frequencies of tau deposits in the OB and EC were highly correlated [29] [36], indicating that both NPTs and NFTs appear in the olfactory system as early as they do in the EC. Although a recent animal model study reported the correlation of olfactory dysfunction with Ab burden in the OB and piriform cortex [37], further research is needed to establish the relationship between the appearance of AD pathology in the olfactory neural network and olfactory function in humans. "
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    ABSTRACT: Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and AD.” The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.
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    • "It is also known that the presence of temporoparietal regional cerebral blood flow (rCBF) deficits on single photon emission computed tomography (SPECT) increases the accuracy of the clinical diagnosis in patients with probable AD [17]. It was also suggested that decreased olfactory identification in MCI may be a marker for the early diagnosis of Alzheimer's disease, but the predictive diagnostic utility of these markers has not been confirmed [4]. Furthermore, the clinical utility of previously proposed peripheral markers (platelets, lymphocytes and pupil dilation test) [35] is questionable. "

    Full-text · Dataset · Jun 2013
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    • "Such changes implicate cholinergic modulation of the bulb in behavioral responses to odors. Further, the concurrent disruption in both the cholinergic innervation and olfaction early during neurodegenerative diseases like Alzheimer's disease [12], [13], suggests an important role for this centrifugal input. "
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    ABSTRACT: The interplay between olfactory activity and cholinergic modulation remains to be fully understood. This report examines the pattern of cholinergic innervation throughout the murine main olfactory bulb across different developmental stages and in naris-occluded animals. To visualize the pattern of cholinergic innervation, we used a transgenic mouse model, which expresses a fusion of the microtubule-associated protein, tau, with green fluorescence protein (GFP) under the control of the choline acetyltransferase (ChAT) promoter. This tau-GFP fusion product allows for a remarkably vivid and clear visualization of cholinergic innervation in the main olfactory bulb (MOB). Interestingly, we find an uneven distribution of GFP label in the adult glomerular layer (GL), where anterior, medial, and lateral glomerular regions of the bulb receive relatively heavier cholinergic innervation than other regions. In contrast to previous reports, we find a marked change in the pattern of cholinergic innervation to the GL following unilateral naris occlusion between the ipsilateral and contralateral bulbs in adult animals.
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