Evidence for altered dendritic spine compartmentalization in Alzheimer’s disease and functional effects in a mouse model
Acta Neuropathol. 2018-04-25; 135(6): 839-854
DOI: 10.1007/s00401-018-1847-6
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1. Acta Neuropathol. 2018 Jun;135(6):839-854. doi: 10.1007/s00401-018-1847-6. Epub
2018 Apr 25.
Evidence for altered dendritic spine compartmentalization in Alzheimer’s disease
and functional effects in a mouse model.
Androuin A(1), Potier B(2)(3), Nägerl UV(4)(5), Cattaert D(6)(5), Danglot L(2),
Thierry M(1), Youssef I(1), Triller A(7), Duyckaerts C(1), El Hachimi KH(1)(8),
Dutar P(2)(3), Delatour B(1), Marty S(9).
Author information:
(1)Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225,
Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.
(2)Centre de Psychiatrie et Neurosciences, INSERM, UMR 894, Université Paris
Descartes, Sorbonne Paris Cité, Paris, France.
(3)Biophotonique et Réseaux Neuronaux, UMR9188 LAC, Université Paris-Sud, Orsay,
France.
(4)Institut Interdisciplinaire de Neurosciences, CNRS UMR 5297, Bordeaux, France.
(5)Université de Bordeaux, Bordeaux, France.
(6)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR
5287, Bordeaux, France.
(7)École Normale Supérieure, Institut de Biologie de l’ENS, INSERM, CNRS, PSL
Research University, Paris, France.
(8)Laboratoire de Neurogénétique, EPHE, PSL Research University, Paris, France.
(9)Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225,
Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.
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Alzheimer’s disease (AD) is associated with a progressive loss of synapses and
neurons. Studies in animal models indicate that morphological alterations of
dendritic spines precede synapse loss, increasing the proportion of large and
short (“stubby”) spines. Whether similar alterations occur in human patients, and
what their functional consequences could be, is not known. We analyzed biopsies
from AD patients and APP x presenilin 1 knock-in mice that were previously shown
to present a loss of pyramidal neurons in the CA1 area of the hippocampus. We
observed that the proportion of stubby spines and the width of spine necks are
inversely correlated with synapse density in frontal cortical biopsies from
non-AD and AD patients. In mice, the reduction in the density of synapses in the
stratum radiatum was preceded by an alteration of spine morphology, with a
reduction of their length and an enlargement of their neck. Serial sectioning
examined with electron microscopy allowed us to precisely measure spine
parameters. Mathematical modeling indicated that the shortening and widening of
the necks should alter the electrical compartmentalization of the spines, leading
to reduced postsynaptic potentials in spine heads, but not in soma. Accordingly,
there was no alteration in basal synaptic transmission, but long-term
potentiation and spatial memory were impaired. These results indicate that an
alteration of spine morphology could be involved in the early cognitive deficits
associated with AD.
DOI: 10.1007/s00401-018-1847-6
PMID: 29696365