TY - JOUR
T1 - Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease
AU - Ardiles, Álvaro O.
AU - Tapia-Rojas, Cheril C.
AU - Mandal, Madhuchhanda
AU - Alexandre, Frédéric
AU - Kirkwood, Alfredo
AU - Inestrosa, Nibaldo C.
AU - Palacios, Adrian G.
PY - 2012/8/21
Y1 - 2012/8/21
N2 - Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-â (Aâ) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aâ oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aâ oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aâ oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated.
AB - Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-â (Aâ) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aâ oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aâ oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aâ oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated.
KW - Aging
KW - Hippocampus
KW - Memory dysfunction
KW - Neural plasticity
KW - T-maze
UR - http://www.scopus.com/inward/record.url?scp=84865305651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865305651&partnerID=8YFLogxK
U2 - 10.1073/pnas.1201209109
DO - 10.1073/pnas.1201209109
M3 - Article
C2 - 22869717
AN - SCOPUS:84865305651
SN - 0027-8424
VL - 109
SP - 13835
EP - 13840
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 34
ER -