Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages

Kovács, Tibor; Cairns, Nigel J.

doi:10.1097/00001756-200102120-00021

Cited by 197 publications

(151 citation statements)

References 18 publications

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“…We thus suggest that spatial information conveyed by the SCs to the hippocampus is likely to remain relatively intact at this early stage of the pathology, while other sensory inputs, including olfactory information processing [30], conveyed by FCs to the hippocampus, might be altered. This conclusion is supported by observing that early olfactory dysfunction has been significantly associated with the risk of future AD and AD neuropathology burden in the brain of mice and patients [12,24,38,52,54]. Our data support the development of investigative methods aiming at detecting the early symptoms of AD on brain function by focusing on the memory processes that involve the LEC region and the subsequent processing of non-spatial stimuli.…”

Section: Functional Implications Of Altered Scs and Fcs Firing Duringsupporting

confidence: 79%

Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model

Marcantoni

Raymond

Carbone

et al. 2013

Pflugers Arch - Eur J Physiol

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The entorhinal cortex (EC) is divided into medial (MEC) and lateral (LEC) anatomical areas and layer II neurons of these two regions project to granule cells of the dentate gyrus (DG) through the medial and lateral perforant pathway (MPP, LPP), respectively. Stellate cells (SCs) represent the main neurons constituting the MPP inputs, while fan cells (FCs) represent the main LPP inputs.Here, we first characterized the excitability properties of SCs and FCs in adult wild-type (WT) mouse brain. Our data indicate that during sustained depolarization, action potentials (APs) generated by SCs exhibit increased fast afterhyperpolarization (fAHP) and overshoot, making them able to fire at higher frequencies and to exhibit higher spike frequency adaptation (SFA) than FCs.Since the EC is one of the earliest brain regions affected during Alzheimer's disease (AD) progression, we compared SCs and FCs firing in 4 months old WT and transgenic Tg2576 mice, a well established AD mouse model. Tg2576-SCs displayed a slight increase in firing frequency during mild depolarization but otherwise normal excitability properties during higher stimulations.On the contrary, Tg2576-FCs exhibited a decreased firing frequency during mild and higher depolarizations, as well as an increased SFA. Our data identify the FCs as a neuronal population particularly sensitive to early pathological effects of chronic accumulation of APP-derived peptides, as occurs in Tg2576 mice. As FCs represent the major input of sensory information to the hippocampus during memory acquisition, early alterations in their excitability profile could significantly contribute to the onset of cognitive decline in AD.

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Section: Functional Implications Of Altered Scs and Fcs Firing Duringsupporting

confidence: 79%

Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model

Marcantoni

Raymond

Carbone

et al. 2013

Pflugers Arch - Eur J Physiol

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“…37,38 In AD, tau-related pathology within these structures correlates with disease severity, cortical Lewy body counts, and apolipoprotein 4 carrier status. 39,40 Superoxide dismutases, enzymes that defend against reactive oxygen species, are abundant in the olfactory bulb, anterior olfactory nucleus, and neuroepithelium of patients with AD, where they are overexpressed relative to control subjects. 41 Increases in other indices of oxidative damage within the olfactory neuroepithelium of patients with AD have also been reported, including heme oxygenase-1, a stress response protein.…”

Section: Centrifugal Afferent Innervation Comes From the Horizontal Lmentioning

confidence: 99%

“…Others suggest the initial pathology may first appear in peripheral olfactory structures. 40,55 The lower density of plaques and tangles in the olfactory bulb and tract than in the amygdala and hippocampus has been interpreted as central to peripheral movement of pathology. 56 For a number of reasons, such observations do not disprove the olfactory vector hypothesis.…”

Section: Centrifugal Afferent Innervation Comes From the Horizontal Lmentioning

confidence: 99%

The olfactory vector hypothesis of neurodegenerative disease: Is it viable?

Doty

2008

Annals of Neurology

344

279

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Environmental agents, including viruses, prions, and toxins, have been implicated in the cause of a number of neurodegenerative diseases, most notably Alzheimer's and Parkinson's diseases. The presence of smell loss and the pathological involvement of the olfactory pathways in the formative stages of Alzheimer's and Parkinson's diseases, together with evidence that xenobiotics, some epidemiologically linked to these diseases, can readily enter the brain via the olfactory mucosa, have led to the hypothesis that Alzheimer's and Parkinson's diseases may be caused or catalyzed by agents that enter the brain via this route. Evidence for and against this concept, the “olfactory vector hypothesis,” is addressed in this review. Ann Neurol 2008;63:7–15

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“…Thus, altered cholesterol homeotasis could contribute to the development of olfactory dysfunction in sporadic AD. Pathologically, oxidative damage, the presence of Aβ plaque, and accumulation of phosphorylated tau as neurofilrillary tangles all have been documented in olfactory epithelium and olfactory bulbs of AD patients [44][45][46][47][48][49][50][51]. Previously we showed in olfactory bulb from cholesterol-fed rabbits that elevated levels of circulating cholesterol disrupted the blood-brain barrier [16], increased accumulations of cholesterol in endolysosomes of neurons in olfactory bulb originated from peripheral sources, and contributed to the development of AD-like pathology including synaptic loss, elevated Aβ production, and increased tau phosphorylation [7].…”

Section: Discussionmentioning

confidence: 99%

Caffeine blocks cholesterol-enriched diet induced AD-like pathology in rabbits

Chen¹,

Tian²,

Ghribi³

et al. 2016

J Integr Syst Neurosci

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The pathogenesis of sporadic AD is believed to result from complex interactions between nutritional, environmental, epigenetic and genetic factors. Among those factors, elevated plasma cholesterol, independent of APOE genotypes, is strongly linked to the pathogenesis of sporadic AD, whereas chronic ingestion of caffeine is protective against sporadic AD. Others and we have shown that rabbits-fed cholesterol-enriched diet exhibit early AD-like pathological features including bloodbrain barrier (BBB) leakage and endolysosome dysfunction, as well as, AD-like pathological hallmarks including synaptic disruption, increased intraneuronal and brain deposition of amyloid beta (Aβ), and tau pathology. Further, we found that caffeine protects against the cholesterol-induced increases in BBB permeability. Here, we determined the extent to which caffeine affects cholesterol-enriched diet-induced increases in other pathological features of AD. We demonstrated that caffeine administration at low and moderate doses did not affect plasma levels of cholesterol, but did block significantly cholesterol-enriched diet-induced increases in brain levels of apoB and accumulation of apoB in neuronal endolysosomes. Furthermore, we demonstrated that caffeine administration at the two doses blocked cholesterol-enriched diet-induced abnormal accumulation of synaptophysin, Aβ, and phosphorylated tau in endolysosomes. Our findings suggest that caffeine exerts its protective effects against the development of sporadic AD-like pathological features, in part, by preventing the entrance of LDL cholesterol into brain parenchyma, the accumulation of LDL-cholesterol in neuronal endolysosomes, and structural and functional changes to endolysosomes.

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Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages

Cited by 197 publications

References 18 publications

Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model

Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model

The olfactory vector hypothesis of neurodegenerative disease: Is it viable?

Caffeine blocks cholesterol-enriched diet induced AD-like pathology in rabbits

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