Premium
Alzheimer’s is associated with neuropathological changes in olfactory bulb that are related to APOE genotype (728.1)
Author(s) -
Parcon Paul,
Aboud Orwa,
Biedermann JoAnn,
Mrak Robert,
Griffin W. Sue
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.728.1
Subject(s) - olfactory bulb , apolipoprotein e , pathology , neuroinflammation , pathological , microglia , olfactory system , biology , olfactory tubercle , olfaction , neuroscience , disease , medicine , inflammation , central nervous system , immunology
Alzheimer patients (AD) may experience changes in olfaction before clinical or neuropathological manifestations. Neuroinflammation, in particular interleukin‐1 (IL‐1), is known to induce each of the precursors of these manifestations. We studied anatomical and pathological features in frozen and paraffin‐embedded tissue sections of olfactory bulbs resected from autopsy tissue of 15 patients (5 APOE ε3,3 neurologically normal, 5 APOE ε3,3 and 5 APOE ε4,4 AD patients) with an age range from 68 to 85 yrs, using fluorescent and western immunochemistry. Compared to control, patients with AD had greater expression of hyper‐phosphorylated tau, particularly in those of APOE ε4,4 genotype compared to ε3,3. These findings were associated with increased expression of IL‐1, and the number of activated microglia was elevated. Furthermore, hyperphosphorylated tau expression was high in neuron cell bodies compared to that in axons in the olfactory tract. Although corpora amylacea were abundant, there was no disease‐related difference in distribution, number, or size. Our findings are consistent with the idea that changes in expression of disease‐associated precursor proteins in olfactory structures and the cytokines that drive their expression are related to APOE genotype and are important elements in the neuroanatomical spread of the neuropathological changes in AD. Grant Funding Source : Supported by NIH/NIA AG12411 and the Windgate Foundation