Decreased expression of GGA3 Protein in Alzheimer's disease frontal cortex and increased co-distribution of BACE with the amyloid precursor protein
Decreased expression of GGA3 Protein in Alzheimer's disease frontal cortex and increased co-distribution of BACE with the amyloid precursor protein
BACE initiates the amyloidogenic processing of the amyloid precursor protein (APP) that results in the production of Aβ peptides associated with Alzheimer's disease (AD). Previous studies have indicated that BACE is elevated in the frontal cortex of AD patients. Golgi-localized γ-ear containing ADP ribosylation factor-binding proteins (GGA) control the cellular trafficking of BACE and may alter its levels. To investigate a link between BACE and GGA expression in AD, frontal cortex samples from AD (N = 20) and healthy, age-matched controls (HC, N =17) were analyzed by immunoblotting. After normalization to the neuronal marker β-tubulin III, the data indicate an average two-fold increase of BACE protein (p = 0.01) and a 64% decrease of GGA3 in the AD group compared to the HC (p = 0.006). GGA1 levels were also decreased in AD, but a statistical significance was not achieved. qRT-PCR analysis of GGA3 mRNA showed no difference between AD and HC. There was a strong correlation between GGA1 and GGA3 in both AD and HC, but no correlation between BACE and GGA levels. Subcellular fractionation of AD cortex with low levels of GGA proteins showed an alteration of BACE distribution and extensive co-localization with APP. These data suggest that altered compartmentalization of BACE in AD promotes the amyloidogenic processing of APP.
- University of Melbourne Australia
- The Alfred Hospital Australia
- Florey Institute of Neuroscience and Mental Health Australia
- Victoria University Australia
Central Nervous System, Male, brain health, 610, Down-Regulation, Neurosciences. Biological psychiatry. Neuropsychiatry, amyloid precursor protein, Amyloid beta-Protein Precursor, Alzheimer Disease, 616, Aspartic Acid Endopeptidases, Humans, BACE, GGA, Aged, Aged, 80 and over, PrP, Neurodegenerative Disorders Related to Ageing, AD, BACE1, Secretase, Alzheimer's disease, Middle Aged, 3207 Medical microbiology, Frontal Lobe, Up-Regulation, Adaptor Proteins, Vesicular Transport, Chancellery, prion protein, Amyloid precursor protein, Nerve Degeneration, Female, Amyloid Precursor Protein Secretases, immunoblotting, Cellular Nervous System, dementia, RC321-571, trans-Golgi Network
Central Nervous System, Male, brain health, 610, Down-Regulation, Neurosciences. Biological psychiatry. Neuropsychiatry, amyloid precursor protein, Amyloid beta-Protein Precursor, Alzheimer Disease, 616, Aspartic Acid Endopeptidases, Humans, BACE, GGA, Aged, Aged, 80 and over, PrP, Neurodegenerative Disorders Related to Ageing, AD, BACE1, Secretase, Alzheimer's disease, Middle Aged, 3207 Medical microbiology, Frontal Lobe, Up-Regulation, Adaptor Proteins, Vesicular Transport, Chancellery, prion protein, Amyloid precursor protein, Nerve Degeneration, Female, Amyloid Precursor Protein Secretases, immunoblotting, Cellular Nervous System, dementia, RC321-571, trans-Golgi Network
36 Research products, page 1 of 4
- 2018IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).36 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
