Wesson DW, Levy E, Nixon RA, Wilson DA.
Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model.
J Neurosci. 2010 Jan 13;30(2):505-14.
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From my standpoint, the main news of the Wilson study (no relation) is the finding that the olfactory bulb was the first site of amyloid deposition in the brain. Pathological studies of aged humans have shown central olfactory regions to be early sites of AD pathologic changes, but most attention has focused on olfactory cortical areas, especially entorhinal cortex. The findings, if applicable to humans, reinforce the idea that olfactory dysfunction is a very early sign of the disease which may prove helpful, in combination with other markers, in detecting affected persons before the disease has caused widespread damage to the brain.
Impaired olfaction is also a very early sign of PD, but its pathologic basis has been difficult to establish. The Wattendorf study in a very small group of PD patients and controls found impaired olfaction in PD to be associated with atrophy in central olfactory regions (i.e., piriform cortex and amygdala). Better understanding of the pathological basis of this deficit could substantially help with early detection of PD.
At this point, the implications of these findings are mainly for research, because without disease-altering treatments, the clinical need for early diagnosis is limited. In the meantime, we need more longitudinal and clinical-pathologic research on olfaction in humans.
Interesting paper and nice to see some experimental work being done in this area. I would like to refer readers in this field to our recent papers (below), which confirm earlier work by several investigators that olfactory bulb is universally affected in Parkinson disease as well as dementia with Lewy bodies and other Lewy body disorders. In an autopsy series of normal elderly subjects as well as subjects with Alzheimer disease, Lewy bodies and associated synuclein-immunoreactive fibers were found in many cases to be present only in the olfactory bulb, suggesting that olfactory bulb involvement is the first stage of Lewy body disease.
Beach TG, White CL, Hladik CL, Sabbagh MN, Connor DJ, Shill HA, Sue LI, Sasse J, Bachalakuri J, Henry-Watson J, Akiyama H, Adler CH, .
Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.
Acta Neuropathol. 2009 Feb;117(2):169-74.
Beach TG, Adler CH, Lue L, Sue LI, Bachalakuri J, Henry-Watson J, Sasse J, Boyer S, Shirohi S, Brooks R, Eschbacher J, White CL, Akiyama H, Caviness J, Shill HA, Connor DJ, Sabbagh MN, Walker DG, .
Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction.
Acta Neuropathol. 2009 Jun;117(6):613-34.
I know it was a long time ago, but just for the record: One of the first and perhaps one of the most comprehensive studies on olfactory dysfunction in AD was published by an MA student of mine and myself in 1986 (Knupfer and Spiegel: Differences in olfactory test performance between normal aged, Alzheimer and vascular type dementia individuals. Int. J. Geriat. Psychiat. 1: 3-13; 1986). It is rewarding to see that there are now mouse models to simulate the pathophysiology of this relatively early, albeit unspecific sign of AD pathology.
In Alzheimer disease, a diminished sense of smell and memory impairment are partly the results of oxidative damage done to olfactory and muscarinic receptors, respectively (both are G protein-coupled receptors). Polyphenols help restore the sense of smell and improve short-term memory in three ways: They promote the neurogenesis of the olfactory bulb and nerve cells in the hippocampus, they prevent further oxidative stress, and they partially restore the function of olfactory and muscarinic receptors by adding hydrogen back to G proteins. The smelling of polyphenolic/aromatic compounds may well play an important role in the treatment of Alzheimer disease.
Alkam T, Nitta A, Mizoguchi H, Itoh A, Nabeshima T.
A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).
Behav Brain Res. 2007 Jun 18;180(2):139-45.
Valente T, Hidalgo J, Bolea I, Ramirez B, Anglés N, Reguant J, Morelló JR, Gutiérrez C, Boada M, Unzeta M.
A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain.
J Alzheimers Dis. 2009;18(4):849-65.