Synaptic pathology in prefrontal cortex is present only with severe dementia in Alzheimer disease.
Synaptic pathology is proposed to be integral to the clinical expression of Alzheimer disease (AD). Most studies have assessed only the vesicle protein synaptophysin as a measure of synaptic integrity. The interrelationships of synaptophysin, other presynaptic proteins, the cholinergic system, and severity of dementia in AD remain unclear. We studied the presynaptic proteins synaptophysin, syntaxin and SNAP-25, along with choline acetyltransferase (ChAT) activity in prefrontal cortex (BA 46) samples from 18 subjects with AD and 16 controls. Mean values of presynaptic protein immunoreactivities were significantly reduced, by 21%-28%, and ChAT activity was reduced by 41% in the AD groups. Synaptic protein immunoreactivity and ChAT activity were correlated with Mini-Mental State Examination scores obtained 1 yr prior to death. When AD cases were subgrouped into mild/moderate and severe illness at time of death, all differences in presynaptic proteins and ChAT activity were significant between controls and severe cases. However, no significant differences were detected in BA 46 between controls and mild/moderate cases. Considerable synaptic reserve or plasticity remains in BA 46 until the late stages of AD. Synaptophysin and ChAT appear to be more vulnerable in severe AD than are syntaxin or SNAP-25.
Minger
S L
SL
Dementia Research Laboratory, Neuroscience Research Centre, GKT School of Biomedical Sciences, King's College London, United Kingdom.
Honer
W G
WG
Esiri
M M
MM
McDonald
B
B
Keene
J
J
Nicoll
J A
JA
Carter
J
J
Hope
T
T
Francis
P T
PT
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology* / Q000523:psychology; D000704:Analysis of Variance; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000201:enzymology / Q000473:pathology*; D017729:Presynaptic Terminals / Q000201:enzymology / Q000473:pathology*; D050765:Qa-SNARE Proteins; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013569:Synapses / Q000201:enzymology / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; C494208:SNAP25 protein, human; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D002795:Choline O-Acetyltransferase