Neurochemical dissection of synaptic pathology in Alzheimer's disease.
Synaptic pathology has attained increasing attention as being central in the pathogenesis of Alzheimer's disease (AD). To address the question whether synaptic pathology in AD involves the whole synapse, or is limited to specific components thereof, we studied three different synaptic vesicle proteins (rab3a, synaptotagmin, synaptophysin) and also the presynaptic membrane protein GAP-43 and the postsynaptic protein neurogranin. The material included postmortem brain tissue (frontal cortex, hippocampus, and cerebellum) from 8 patients with early-onset AD (EAD), 11 patients with late-onset AD (LAD), 6 patients with vascular dementia (VAD), and 9 control subjects. A reduction of all synaptic proteins was found in AD, more pronounced in EAD than in LAD, in both the frontal cortex (EAD 30% to 70% vs. LAD 82% to 88% of control value) and hippocampus (EAD 22% to 82% vs. LAD 76% to 89% of control value), whereas only minor changes were found in VAD. The finding that all synaptic proteins were reduced in AD suggests a degeneration and loss of whole synaptic elements that are more pronounced in EAD than in LAD.
Davidsson
P
P
Department of Clinical Neuroscience, Sahlgrenska University Hospital, Mölndal, Sweden. pia.davidsson@ms.se
Blennow
K
K
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000473:pathology*; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D016022:Case-Control Studies; D002531:Cerebellum / Q000737:chemistry / Q000473:pathology; D015140:Dementia, Vascular / Q000473:pathology; D005625:Frontal Lobe / Q000737:chemistry* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000032:analysis; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D017729:Presynaptic Terminals / Q000737:chemistry; D012720:Severity of Illness Index; D013569:Synapses / Q000737:chemistry / Q000473:pathology*; D013570:Synaptic Membranes / Q000737:chemistry; D013572:Synaptic Vesicles / Q000737:chemistry
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D019204:GTP-Binding Proteins