Decreased presence of perforated synapses in a triple-transgenic mouse model of Alzheimer's disease.
Transgenic mouse models of Alzheimer's disease (AD) are useful tools to further our understanding of AD genotype-phenotype interaction. The triple transgenic mice harboring mutant forms of APP/PS1/Tau (3xTg-AD) exhibit beta-amyloid (Abeta) plaques (by 6 months of age) as well as neurofibrillary tangles (by 10-12 months of age). In this study, we characterized morphological alterations of hippocampal synapses obtained from 13-month-old 3xTg-AD and age-matched control (PS1-KI) mice. Numeric density of synapses (Nv, number of junctions/microm(3) of tissue), average synaptic contact area (S), and synaptic surface density (Sv, total synaptic contact area/microm(3) of tissue) were investigated by morphometric methods in the AD vulnerable CA1 pyramidal cell layer. Comparisons between 3xTg-AD and control mice showed no statistically significant differences in any of the three parameters; however, a significant decrease (by 28.5%) in the fraction of perforated junctional areas (PS) was observed in the 3xTg-AD mice. As PS is a reliably indirect index of synaptic plasticity, a decreased PS number might represent a subtle and early sign of synaptic dysfunction occurring in the 3xTg-AD mice, and lend support to the hypothesis that altered synaptic function is a critical feature of AD.
Bertoni-Freddari
Carlo
C
Neurobiology of Aging Laboratory, INRCA Research Department, Ancona, Italy. c.bertoni@inrca.it
Sensi
Stefano L
SL
Giorgetti
Belinda
B
Balietti
Marta
M
Di Stefano
Giuseppina
G
Canzoniero
Lorella M T
LM
Casoli
Tiziana
T
Fattoretti
Patrizia
P
D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure