Immunolocalization of apolipoprotein E (apoE) was investigated in human olfactory mucosa in which olfactory receptor neurons (ORNs) were identified with antiserum to protein gene product (PGP) 9.5. Tissue was obtained at autopsy from 10 nondemented middle-aged or elderly subjects and 9 patients with Alzheimer's disease (AD). Double-labeling immunofluorescence established that apoE immunoreactivity was colocalized in a subpopulation of PGP 9.5-immunoreactive ORNs. The mean number of apoE-immunoreactive ORNs per unit epithelial length in AD patients was about 3.5 times greater than that in nondemented patients, although the mean number of PGP 9.5-immunoreactive ORNs was similar. The apoE-immunopositive Schwann cells in olfactory nerve bundles were the probable source of apoE in the ORNs. The increased numbers of apoE-immunoreactive ORNs in AD patients compared to nondemented subjects demonstrates another manifestation of AD-related neuropathology, in addition to cytoskeletal changes, β-amyloid deposition, and changes in immunoreactivity for other neuroproteins, that parallels changes in neurons in the AD brain.
MahleyRW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science1988; 240: 622–30.
2.
PoirierJ. Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease. Trends Neurosci1994; 17: 525–30.
3.
StrittmatterWJRosesAD. Apolipoprotein E and Alzheimer disease. Proc Natl Acad Sci USA1995; 92: 4725–7.
4.
NambaYTomonagaMKawasakiHOtomoEIkedaK. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res1991; 541: 163–6.
5.
RebeckGWReiterJSStricklandDKHymanBT. Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron1993; 11: 575–80.
6.
HanSHuletteCSaundersAM. Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer's disease and in age-matched controls. Exp Neurol1994; 128: 13–26.
7.
BenzingWCMufsonEJ. Apolipoprotein E immunoreactivity within neurofibrillary tangles: relationship to tau and PHF in Alzheimer's disease. Exp Neurol1995; 132: 162–71.
8.
MetzgerRELaDuMJPanJBGetzGSFrailDEFaldutoMT. Neurons of the human frontal cortex display apolipoprotein E immunoreactivity: implications for Alzheimer's disease. J Neuropathol Exp Neurol1996; 55: 372–80.
9.
SchmechelDESaundersAMStrittmatterWJ. Increased amyloid, β-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA1993; 90: 9649–53.
10.
StrittmatterWJSaundersAMGoedertM. Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. Proc Natl Acad Sci USA1994; 91: 11183–6.
11.
HuangDYGoedertMJakesR. Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease. Neurosci Lett1994; 182: 55–8.
12.
MurphyCGilmoreMMSeeryCSSalmonDPLaskerBR. Olfactory thresholds are associated with degree of dementia in Alzheimer's disease. Neurobiol Aging1990; 11: 465–9.
13.
DotyRL. Olfactory dysfunction in neurodegenerative disorders. In: GetchellTVDotyRLBartoshukLMSnowJBJr, eds. Smell and taste in health and disease. New York, NY: Raven Press, 1991: 735–51.
DaviesDCBrooksJWLewisDA. Axonal loss from the olfactory tracts in Alzheimer's disease. Neurobiol Aging1993; 14: 353–7.
16.
TalamoBRRudelRKosikKS. Pathological changes in olfactory neurons in patients with Alzheimer's disease. Nature1989; 337: 736–9.
17.
TrojanowskiJQNewmanPDHillWDLeeVM-Y. Human olfactory epithelium in normal aging, Alzheimer's disease, and other neurodegenerative disorders. J Comp Neurol1991; 310: 365–76.
18.
LeeJHGoedertMHillWDLeeVM-YTrojanowskiJQ. Tau proteins are abnormally expressed in olfactory epithelium of Alzheimer patients and developmentally regulated in human fetal spinal cord. Exp Neurol1993; 121: 93–105.
19.
YamagishiMIshizukaYSekiK. Pathology of olfactory mucosa in patients with Alzheimer's disease. Ann Otol Rhinol Laryngol1994; 103: 421–7.
20.
CrinoPBMartinJAHillWDGreenbergBLeeVM-YTrojanowskiJQ. β-Amyloid peptide and amyloid precursor proteins in olfactory mucosa of patients with Alzheimer's disease, Parkinson's disease, and Down syndrome. Ann Otol Rhinol Laryngol1995; 104: 655–61.
GetchellTVKrishnaNS RamaDhooperNSparksLDGetchellML. Human olfactory receptor neurons express heat shock protein 70: age-related trends. Ann Otol Rhinol Laryngol1995; 104: 47–56.
23.
YamagishiMTakamiSGetchellTV. Ontogenetic expression of spot 35 protein (calbindin-D28k) in human olfactory receptor neurons and its decrease in Alzheimer's disease patients. Ann Otol Rhinol Laryngol1996; 105: 132–9.
24.
Kulkarni-NarlaAGetchellTVSchmittFAGetchellML. Manganese and copper-zinc superoxide dismutases in the human olfactory mucosa: increased immunoreactivity in Alzheimer's disease. Exp Neurol1996; 140: 115–25.
25.
SchmittFASanoMC. Neuropsychological approaches to the study of dementia. In: MorrisJC, ed. Handbook of dementing illnesses. New York, NY: Marcel Dekker, 1994: 89–123.
26.
KhachaturianZS. Diagnosis of Alzheimer's disease. Arch Neurol1985; 42: 1097–105.
27.
GetchellTVChenYStrotmannJBreerHGetchellML. Expression of a mucociliary-specific epitope in human olfactory epithelium. Neuroreport1993; 4: 623–6.
28.
HamiltonRLWongJSGuoLSKrisansSHavelRJ. Apolipoprotein E localization in rat hepatocytes by immunogold labeling of cryothin sections. J Lipid Res1990; 31: 1589–603.
29.
TakamiSGetchellMLChenY. Vomeronasal epithelial cells of the adult human express neuron-specific molecules. Neuroreport1993; 4: 375–8.
30.
NakashimaTKimmelmanCPSnowJBJr.Immunohistopathology of human olfactory epithelium, nerve and bulb. Laryngoscope1985; 95: 391–6.
31.
RosesAD. Apolipoprotein E is a relevant susceptibility gene that affects the rate of expression of Alzheimer's disease. Neurobiol Aging1994; 15(Suppl 2): S165–S167.
32.
GetchellMLGetchellTV. Differential expression of cell-specific molecules in olfactory receptor neurons of humans of different ages. In: KuriharaKSuzukiNOgawaH, eds. Olfaction and taste XI. Tokyo, Japan: Springer-Verlag, 1994: 602–3.
33.
HuangDYWeisgraberKHStrittmatterWJMatthewWD. Interaction of apolipoprotein E with laminin increases neuronal adhesion and alters neurite morphology. Exp Neurol1995; 136: 251–7.
