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Localization of gamma‐secretase subunit Aph‐1 in the central nervous system of Alzheimer's disease mouse model
Author(s) -
He Guiqiong,
Sun Shanquan
Publication year - 2012
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.26.1_supplement.920.4
Subject(s) - presenilin , olfactory bulb , central nervous system , biology , hippocampus , neuroscience , amyloid precursor protein , genetically modified mouse , striatum , brainstem , alzheimer's disease , transgene , pathology , medicine , disease , dopamine , gene , biochemistry
The gamma‐secretase complex cleaves the final step of amyloid protein precursor (APP) to generate amyloid beta peptide (Abeta), a pathogenic component of senile plaques (SP) in the brain of Alzheimer's disease (AD). Recent studies show that Aph‐1 along with presenilins (PS), nicastrin, Pen‐2 are essential components of the gamma‐secretase. The structure and function of Aph‐1 in vitro are well defined, but less is known about its localization in the central nervous system (CNS) of AD model mice. Using Western blot and immunohistochemical methods, we found that APH‐1 is widely expressed at select neuronal populations of major areas (including cortex, hippocampus, olfactory bulb, hypothalamus, striatum, cerebellum, brainstem and spinal cord) in both APP/PS1 double transgenic AD model mice and its wildtype controls. The Aph‐1 expression level is relatively high in the brain at the early stages of postnatal development, but declined gradually to reach adult profiles in both AD and control mice. Aph‐1 is distributed much more extensively than circumscribed SP in AD mice. Aph‐1 expression level is higher than that in control mice. The present study provides an anatomical basis for indicating that APH‐1 is tightly related to AD pathogenesis. This work was supported by National Natural Science Foundation of China (30700885), Key project of Chinese Ministry of Education(209102