Synaptic dysfunction in Alzheimer's disease

Elena Marcello, Roberta Epis, Claudia Saraceno, Monica Di Luca

Research output: Chapter in Book/Report/Conference proceedingChapter

61 Citations (Scopus)

Abstract

Generation of amyloid peptide (Aβ) is at the beginning of a cascade that leads to Alzheimer's disease (AD). Amyloid precursor protein (APP), as well as β- and γ-secretases, is the principal player involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. Recent studies suggested that soluble assembly states of Aβ peptides can cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Therefore, current research investigates the relative importance of these various soluble Aβ assemblies in causing synaptic dysfunction and cognitive deficits. Several Aβ oligomers targets and cellular mechanisms responsible of Aβ-induced synaptic failure have been identified. The first and most important mechanism impugns a toxic gain of function for Aβ which results due to self-association and attainment of new structures capable of novel interactions that lead to impaired plasticity. Other scenarios predicate that Aβ has a normal physiological role. On the one hand, insufficient Aβ could lead to a loss of normal function, whereas excess Aβ may precipitate dysfunction. How this occurs and which the main target/s is/are for the synaptic action of Aβ remains to be fully understood and would certainly represent one of the main challenges to future AD research.

Original languageEnglish
Title of host publicationSynaptic Plasticity: Dynamics, Development and Disease
Pages573-601
Number of pages29
Volume970
DOIs
Publication statusPublished - 2012

Publication series

NameAdvances in Experimental Medicine and Biology
Volume970
ISSN (Print)00652598

Fingerprint

Amyloid Precursor Protein Secretases
Amyloid beta-Protein Precursor
Alzheimer Disease
Poisons
Research
Amyloid
Oligomers
Peptides
Plasticity
Precipitates
peptide A
Cognitive Dysfunction

Keywords

  • Alzheimer's disease
  • Amyloid ß
  • Amyloid Precursor Protein
  • Glutamate receptors
  • Secretases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Marcello, E., Epis, R., Saraceno, C., & Di Luca, M. (2012). Synaptic dysfunction in Alzheimer's disease. In Synaptic Plasticity: Dynamics, Development and Disease (Vol. 970, pp. 573-601). (Advances in Experimental Medicine and Biology; Vol. 970). https://doi.org/10.1007/978-3-7091-0932-8_25

Synaptic dysfunction in Alzheimer's disease. / Marcello, Elena; Epis, Roberta; Saraceno, Claudia; Di Luca, Monica.

Synaptic Plasticity: Dynamics, Development and Disease. Vol. 970 2012. p. 573-601 (Advances in Experimental Medicine and Biology; Vol. 970).

Research output: Chapter in Book/Report/Conference proceedingChapter

Marcello, E, Epis, R, Saraceno, C & Di Luca, M 2012, Synaptic dysfunction in Alzheimer's disease. in Synaptic Plasticity: Dynamics, Development and Disease. vol. 970, Advances in Experimental Medicine and Biology, vol. 970, pp. 573-601. https://doi.org/10.1007/978-3-7091-0932-8_25
Marcello E, Epis R, Saraceno C, Di Luca M. Synaptic dysfunction in Alzheimer's disease. In Synaptic Plasticity: Dynamics, Development and Disease. Vol. 970. 2012. p. 573-601. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-3-7091-0932-8_25
Marcello, Elena ; Epis, Roberta ; Saraceno, Claudia ; Di Luca, Monica. / Synaptic dysfunction in Alzheimer's disease. Synaptic Plasticity: Dynamics, Development and Disease. Vol. 970 2012. pp. 573-601 (Advances in Experimental Medicine and Biology).
@inbook{a68feb270a0546c289c8d13dd1138af2,
title = "Synaptic dysfunction in Alzheimer's disease",
abstract = "Generation of amyloid peptide (Aβ) is at the beginning of a cascade that leads to Alzheimer's disease (AD). Amyloid precursor protein (APP), as well as β- and γ-secretases, is the principal player involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. Recent studies suggested that soluble assembly states of Aβ peptides can cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Therefore, current research investigates the relative importance of these various soluble Aβ assemblies in causing synaptic dysfunction and cognitive deficits. Several Aβ oligomers targets and cellular mechanisms responsible of Aβ-induced synaptic failure have been identified. The first and most important mechanism impugns a toxic gain of function for Aβ which results due to self-association and attainment of new structures capable of novel interactions that lead to impaired plasticity. Other scenarios predicate that Aβ has a normal physiological role. On the one hand, insufficient Aβ could lead to a loss of normal function, whereas excess Aβ may precipitate dysfunction. How this occurs and which the main target/s is/are for the synaptic action of Aβ remains to be fully understood and would certainly represent one of the main challenges to future AD research.",
keywords = "Alzheimer's disease, Amyloid {\ss}, Amyloid Precursor Protein, Glutamate receptors, Secretases",
author = "Elena Marcello and Roberta Epis and Claudia Saraceno and {Di Luca}, Monica",
year = "2012",
doi = "10.1007/978-3-7091-0932-8_25",
language = "English",
isbn = "9783709109311",
volume = "970",
series = "Advances in Experimental Medicine and Biology",
pages = "573--601",
booktitle = "Synaptic Plasticity: Dynamics, Development and Disease",

}

TY - CHAP

T1 - Synaptic dysfunction in Alzheimer's disease

AU - Marcello, Elena

AU - Epis, Roberta

AU - Saraceno, Claudia

AU - Di Luca, Monica

PY - 2012

Y1 - 2012

N2 - Generation of amyloid peptide (Aβ) is at the beginning of a cascade that leads to Alzheimer's disease (AD). Amyloid precursor protein (APP), as well as β- and γ-secretases, is the principal player involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. Recent studies suggested that soluble assembly states of Aβ peptides can cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Therefore, current research investigates the relative importance of these various soluble Aβ assemblies in causing synaptic dysfunction and cognitive deficits. Several Aβ oligomers targets and cellular mechanisms responsible of Aβ-induced synaptic failure have been identified. The first and most important mechanism impugns a toxic gain of function for Aβ which results due to self-association and attainment of new structures capable of novel interactions that lead to impaired plasticity. Other scenarios predicate that Aβ has a normal physiological role. On the one hand, insufficient Aβ could lead to a loss of normal function, whereas excess Aβ may precipitate dysfunction. How this occurs and which the main target/s is/are for the synaptic action of Aβ remains to be fully understood and would certainly represent one of the main challenges to future AD research.

AB - Generation of amyloid peptide (Aβ) is at the beginning of a cascade that leads to Alzheimer's disease (AD). Amyloid precursor protein (APP), as well as β- and γ-secretases, is the principal player involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. Recent studies suggested that soluble assembly states of Aβ peptides can cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Therefore, current research investigates the relative importance of these various soluble Aβ assemblies in causing synaptic dysfunction and cognitive deficits. Several Aβ oligomers targets and cellular mechanisms responsible of Aβ-induced synaptic failure have been identified. The first and most important mechanism impugns a toxic gain of function for Aβ which results due to self-association and attainment of new structures capable of novel interactions that lead to impaired plasticity. Other scenarios predicate that Aβ has a normal physiological role. On the one hand, insufficient Aβ could lead to a loss of normal function, whereas excess Aβ may precipitate dysfunction. How this occurs and which the main target/s is/are for the synaptic action of Aβ remains to be fully understood and would certainly represent one of the main challenges to future AD research.

KW - Alzheimer's disease

KW - Amyloid ß

KW - Amyloid Precursor Protein

KW - Glutamate receptors

KW - Secretases

UR - http://www.scopus.com/inward/record.url?scp=84858120639&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858120639&partnerID=8YFLogxK

U2 - 10.1007/978-3-7091-0932-8_25

DO - 10.1007/978-3-7091-0932-8_25

M3 - Chapter

SN - 9783709109311

VL - 970

T3 - Advances in Experimental Medicine and Biology

SP - 573

EP - 601

BT - Synaptic Plasticity: Dynamics, Development and Disease

ER -