Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PS1 genes.
Post-mortem cortices from patients diagnosed with Alzheimer's disease (AD) exhibit reduced levels of drebrin, an F-actin binding protein of dendritic spines and shafts. We used a mouse model of familial AD (FAD) to determine whether the density of cortical spines engaged in asymmetric (presumably excitatory) synapses and containing drebrin A is reduced and if so, whether this occurs prior to the emergence of beta amyloid deposits, when only soluble beta amyloid (Abeta) is present. Quantitative electron microscopic immunocytochemistry revealed that by 6 months, the proportion of postsynaptic spines with drebrin A within somatosensory cortex layer I was smaller for the FAD model mice, when compared to the corresponding region of WT mice (P < 0.0005). However, the areal density of postsynaptic spines containing drebrin A was relatively constant from 3 to 18 months and beyond for both genotypes, suggesting that drebrin A confers stability to postsynaptic spines. Further measurements confirmed that the reduced proportion of drebrin A-containing spines in brains of FAD mice at 6 months is due to the greater size and areal density of spine profiles lacking drebrin A. Thus, soluble Abeta could affect spines lacking drebrin A more strongly than spines containing drebrin A. At 6 months and older, a larger fraction of spinous drebrin A in 2xKI mice was located near the synaptic membrane, as compared to those of WT mice. This pattern may reflect an altered trafficking of synaptic molecules within spines, a factor adding to the decline of synaptic function and plasticity.
Mahadomrongkul
Veeravan
V
Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA.
Huerta
Patricio T
PT
Shirao
Tomoaki
T
Aoki
Chiye
C
D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D016555:Matched-Pair Analysis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009479:Neuropeptides / Q000378:metabolism*; D053764:Presenilin-1; D013003:Somatosensory Cortex / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D009479:Neuropeptides; D053764:Presenilin-1; C053386:drebrins