Decreased levels of synaptosomal associated protein 25 in the brain of patients with Down syndrome and Alzheimer's disease.
Synaptosomal associated protein 25 kDa (snap-25) is a widely distributed membrane-associated protein in the brain, mainly localized in nerve terminals. In nerve terminals, snap-25 participates in docking and/or fusion of synaptic vesicles with the plasmalemma, a process essential for synaptic vesicle exocytosis. Recent work suggests a role in brain development, forming presynaptic sites by regulating axonal outgrowth and nerve growth-induced neurite elongation. In Down syndrome (DS) brain, it is abnormally developed from early life, and brain pathology becomes even more pronounced when Alzheimer's disease (AD) develops in the fourth decade. This information led us to examine snap-25 in the brain of patients with DS and AD. We studied snap-25 and glial fibrillary acidic protein (GFAP) brain levels in five individual brain areas of 9 aged patients with DS, 9 patients with AD and 9 controls, applying two-dimensional gel electrophoresis. Decreased snap-25 levels were found in the five brain regions of the patients with DS and AD. Increased expression levels of GFAP were found in the frontal, parietal, temporal and occipital cortex regions of the DS and AD patients. Decreased snap-25 protein levels in the brain of DS and AD may reflect impaired synaptogenesis or represent neuronal loss. Findings of increased GFAP, a marker for neuronal loss, along with data from literature would support the notion of decreased snap-25 secondary to neuronal decay in both neurodegenerative disorders.
Greber
S
S
University of Vienna, Department of Pediatrics, Austria.
Lubec
G
G
Cairns
N
N
Fountoulakis
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D013574:Synaptosomes / Q000737:chemistry
D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25