TY  - JOUR
AU  - Ambrad Giovannetti, Eleonora
AU  - Fuhrmann, Martin
TI  - Unsupervised excitation: GABAergic dysfunctions in Alzheimer's disease.
JO  - Brain research
VL  - 1707
SN  - 0006-8993
CY  - Amsterdam
PB  - Elsevier
M1  - DZNE-2020-06847
SP  - 216-226
PY  - 2019
AB  - Alzheimer's disease (AD) is characterized by the classical hallmarks of Aβ-deposition and tau-pathology that are thought to ultimately lead to synapse and neuron loss. Although long known, neuroinflammation has recently attracted a substantial amount of attention by researchers due to genome wide association studies (GWAS) that identified microglia associated genes to be correlated with sporadic AD. Besides that, cholinergic degeneration and gamma-aminobutyric acid (GABA) abnormalities have been identified in the brains of AD patients already decades ago, but have not received much attention over the last ten years. Recently, the neuronal network dysfunction hypothesis has revived interest in how impairments of neuronal communication at the network level lead to epileptiform activity and disrupted oscillations observed in the brains of AD patients and mouse models. Thereby, deficits in neuronal networks involved in learning and memory might ultimately cause memory impairments. In this context, an imbalance between excitation and inhibition has been hypothesized to contribute to neuronal network dysfunction. Here, disturbances of cholinergic and GABAergic transmission might play a crucial role. In this review, we will focus on GABAergic dysfunction in AD and mouse models of AD and how those might relate to neuronal network aberration and memory impairment.
KW  - Alzheimer Disease: physiopathology
KW  - Amyloid beta-Peptides: metabolism
KW  - Animals
KW  - Brain: metabolism
KW  - Disease Models, Animal
KW  - GABAergic Neurons: metabolism
KW  - Humans
KW  - Memory: physiology
KW  - Memory Disorders: pathology
KW  - Nerve Degeneration: pathology
KW  - Nerve Net: physiopathology
KW  - Neurons: metabolism
KW  - gamma-Aminobutyric Acid: metabolism
KW  - tau Proteins: metabolism
LB  - PUB:(DE-HGF)16
C6  - pmid:30503351
DO  - DOI:10.1016/j.brainres.2018.11.042
UR  - https://pub.dzne.de/record/140525
ER  -