Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease

Pamela J. Yao, Min Zhu, Eunice I. Pyun, Andrew I. Brooks, Stavros Therianos, Victoria E. Meyers, Paul Coleman

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Loss of synapses correlates with cognitive decline in Alzheimer's disease (AD). However, molecular mechanisms underlying the synaptic dysfunction and loss are not well understood. In this study, microarray analysis of brain tissues from five AD cases revealed a reduced expression of a group of related genes, all of which are involved in synaptic vesicle (SV) trafficking. By contrast, several synaptic genes with functions other than vesicle trafficking remained unchanged. Quantitative RT-PCR confirmed and expanded the microarray findings. Furthermore, immunoblotting showed that the protein level of at least one of these gene products, dynamin I, correlated with its reduced transcript. Immunhistochemical analysis exhibited an altered distribution of dynamin I immunolabeling in AD neurons. Microarray analysis of transgenic mice with mutated amyloid precursor protein showed that although the transcript levels for some of the SV trafficking-related genes are also decreased, the change in dynamin did not replicate the AD pattern. The results suggest a link among SV vesicle-trafficking pathways, synaptic malfunction, and AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)97-109
Number of pages13
JournalNeurobiology of Disease
Volume12
Issue number2
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Synaptic Vesicles
Frontal Lobe
Alzheimer Disease
Gene Expression
Dynamin I
Genes
Tissue Array Analysis
Dynamins
Amyloid beta-Protein Precursor
Microarray Analysis
Immunoblotting
Synapses
Transgenic Mice
Neurons
Polymerase Chain Reaction
Brain
Proteins

Keywords

  • Alzheimer's disease
  • AP3
  • Clathrin-mediated endocytosis
  • Dynamin
  • Microarray
  • Synapse
  • Synaptic vesicle trafficking

ASJC Scopus subject areas

  • Neurology

Cite this

Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. / Yao, Pamela J.; Zhu, Min; Pyun, Eunice I.; Brooks, Andrew I.; Therianos, Stavros; Meyers, Victoria E.; Coleman, Paul.

In: Neurobiology of Disease, Vol. 12, No. 2, 01.01.2003, p. 97-109.

Research output: Contribution to journalArticle

Yao, Pamela J. ; Zhu, Min ; Pyun, Eunice I. ; Brooks, Andrew I. ; Therianos, Stavros ; Meyers, Victoria E. ; Coleman, Paul. / Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. In: Neurobiology of Disease. 2003 ; Vol. 12, No. 2. pp. 97-109.
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