Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure

In Alzheimer's disease (AD), Amyloid beta (A beta) impairs synaptic function by inhibiting long-term potentiation (LTP), and by facilitating long-term depression (LTD). There is now evidence from AD models that A beta provokes this shift toward synaptic depression by triggering the access to an...

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Autores: Díaz González, Marta, Buberman, Assaf, Morales Fuciños, Miguel, Ferrer, Isidro, Knafo Farhi, Dina Shira
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/51924
Acceso en línea:http://hdl.handle.net/10810/51924
Access Level:acceso abierto
Palabra clave:hippocampus
plasticity
human
cognition
synaptosomes
PSD-95
long-term depression
amyloid-beta
dentate gyrus
dendritic spines
mouse model
disease
memory
phosphatase
retrieval
pathology
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oai_identifier_str oai:addi.ehu.eus:10810/51924
network_acronym_str ES
network_name_str España
repository_id_str
spelling Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network FailureDíaz González, MartaBuberman, AssafMorales Fuciños, MiguelFerrer, IsidroKnafo Farhi, Dina ShirahippocampusplasticityhumancognitionsynaptosomesPSD-95long-term depressionamyloid-betadentate gyrusdendritic spinesmouse modeldiseasememoryphosphataseretrievalpathologyIn Alzheimer's disease (AD), Amyloid beta (A beta) impairs synaptic function by inhibiting long-term potentiation (LTP), and by facilitating long-term depression (LTD). There is now evidence from AD models that A beta provokes this shift toward synaptic depression by triggering the access to and accumulation of PTEN in the postsynaptic terminal of hippocampal neurons. Here we quantified the PTEN in 196,138 individual excitatory dentate gyrus synapses from AD patients at different stages of the disease and from controls with no neuropathological findings. We detected a gradual increase of synaptic PTEN in AD brains as the disease progresses, in conjunction with a significant decrease in synaptic density. The synapses that remain in symptomatic AD patients are more likely to be smaller and exhibit fewer AMPA receptors (AMPARs). Hence, a high A beta load appears to strongly compromise human hippocampal synapses, as reflected by an increase in PTEN, inducing a loss of AMPARs that may eventually provoke synaptic failure and loss.This study was supported by the following agencies: Israel Science Foundation (536/19); Spanish Ministry of Science (Europa Exelencia 15/02, SAF2016-78071-R)Frontiers Media202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/51924reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICINN/SAF2016-78071-R/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144462/info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)Atribución 3.0 Españaoai:addi.ehu.eus:10810/519242026-06-18T09:23:17Z
dc.title.none.fl_str_mv Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
title Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
spellingShingle Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
Díaz González, Marta
hippocampus
plasticity
human
cognition
synaptosomes
PSD-95
long-term depression
amyloid-beta
dentate gyrus
dendritic spines
mouse model
disease
memory
phosphatase
retrieval
pathology
title_short Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
title_full Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
title_fullStr Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
title_full_unstemmed Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
title_sort Aberrant Synaptic PTEN in Symptomatic Alzheimer's Patients May Link Synaptic Depression to Network Failure
dc.creator.none.fl_str_mv Díaz González, Marta
Buberman, Assaf
Morales Fuciños, Miguel
Ferrer, Isidro
Knafo Farhi, Dina Shira
author Díaz González, Marta
author_facet Díaz González, Marta
Buberman, Assaf
Morales Fuciños, Miguel
Ferrer, Isidro
Knafo Farhi, Dina Shira
author_role author
author2 Buberman, Assaf
Morales Fuciños, Miguel
Ferrer, Isidro
Knafo Farhi, Dina Shira
author2_role author
author
author
author
dc.subject.none.fl_str_mv hippocampus
plasticity
human
cognition
synaptosomes
PSD-95
long-term depression
amyloid-beta
dentate gyrus
dendritic spines
mouse model
disease
memory
phosphatase
retrieval
pathology
topic hippocampus
plasticity
human
cognition
synaptosomes
PSD-95
long-term depression
amyloid-beta
dentate gyrus
dendritic spines
mouse model
disease
memory
phosphatase
retrieval
pathology
description In Alzheimer's disease (AD), Amyloid beta (A beta) impairs synaptic function by inhibiting long-term potentiation (LTP), and by facilitating long-term depression (LTD). There is now evidence from AD models that A beta provokes this shift toward synaptic depression by triggering the access to and accumulation of PTEN in the postsynaptic terminal of hippocampal neurons. Here we quantified the PTEN in 196,138 individual excitatory dentate gyrus synapses from AD patients at different stages of the disease and from controls with no neuropathological findings. We detected a gradual increase of synaptic PTEN in AD brains as the disease progresses, in conjunction with a significant decrease in synaptic density. The synapses that remain in symptomatic AD patients are more likely to be smaller and exhibit fewer AMPA receptors (AMPARs). Hence, a high A beta load appears to strongly compromise human hippocampal synapses, as reflected by an increase in PTEN, inducing a loss of AMPARs that may eventually provoke synaptic failure and loss.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/51924
url http://hdl.handle.net/10810/51924
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/SAF2016-78071-R/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144462/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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