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P4‐158: A low‐dose of intravenous immunoglobulin provides protection in focal and global brain ischemia models and abolishes the increased ischemic vulnerability of aged APP/PS1 mice
Author(s) -
Heikkinen Riikka,
Malm Tarja,
Boman Susanna,
Kuhmonen Susanna,
Ahtoniemi Toni,
Muona Anu,
Tanila Heikki,
Koistinaho Jari,
Koistinaho Milla
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.725
Subject(s) - ischemia , medicine , genetically modified mouse , saline , stroke (engine) , lesion , morris water navigation task , pathogenesis , pathology , anesthesia , transgene , hippocampus , biology , mechanical engineering , biochemistry , engineering , gene
Background: BACE initiates the amyloid proteolytic processing of APP that leads to the production of Ab peptides. We have previously reported that BACE levels are increased in the frontal cortex of patients with Alzheimer’s disease (AD). Because no change in BACE mRNA expression was observed, we hypothesized that an alteration of BACE cellular trafficking may be responsible for increased BACE protein and activity in AD. The cellular trafficking of BACE between TNG and endosomes is controlled by Golgi-localized g-ear containing ADP ribosylation factor-binding proteins (GGA). The aim of the present study was to analyse quantitatively the expression GGA1 and GGA3 in frontal cortex of Alzheimer’s disease and control patients in relation to BACE expression. Methods: Frontal cortical samples from AD (N1⁄420), healthy age-matched controls (HC; N1⁄418) and controls with a neurological pathology other than AD (NC; N1⁄48) were homogenized in Trizol to isolate RNA, DNA, and protein. Protein precipitates were analysed by western blotting. Signals were captured with a Syngene DCC imaging system. Statistical analysis was performed using SPSS software (one-way ANOVA) and the results expressed relative to the neuronal marker, b-tubulin III. Results: GGA1 was detected as a 60 kDa doublet. Quantitative analysis indicated that GGA1 levels were decreased by an average of 43% in the AD group compared to the HC (p 1⁄4 0.03). GGA3 was detected as a 75 kDa signal. A 45 kDa species that may represent a caspase cleavage product was also observed in some AD and CT samples. Quantitation of the 75 kDa band indicated a 74% decrease in AD samples compared to HC (p<0.01). Conclusions: This is the first report of simultaneous analysis of GGA1 and GGA3 expression in AD and control brains. A marked decreased expression of both GGA1 and GGA3 was observed and consistent with other reports. Quantitative analysis of BACE with two alternate antibodies and correlation study of GGA and BACE expression are in progress.