Evidence map›Paper›PMID 33573856›Full record

ReviewSeminars in cell & developmental biology2021

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer's disease.

Joan Jiménez-Balado, Teal S Eich

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Seminars in cell & developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
12.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026
    Review
  10. Article
  11. Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Cerebrospinal fluid NPTX2 and [Alzheimer's research & therapy · 2025
    Article

37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Joan Jiménez-BaladoLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Teal S EichLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: teich@usc.edu.
University of Southern California · US

Funding

Exploring the Latent Class Structure of Inhibition in Normal AgingR00AG055684 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EICH, TEAL S · 2019 to 2021
$741k
NIA NIH HHS R00 AG055684
6 · The paper itself

Abstract

In this review, we focus on the potential role of the γ-aminobutyric acidergic (GABAergic) system in age-related episodic memory impairments in humans, with a particular focus on Alzheimer's disease (AD). Well-established animal models have shown that GABA plays a central role in regulating and synchronizing neuronal signaling in the hippocampus, a brain area critical for episodic memory that undergoes early and significant morphologic and functional changes in the course of AD. Neuroimaging research in humans has documented hyperactivity in the hippocampus and losses of resting state functional connectivity in the Default Mode Network, a network that itself prominently includes the hippocampus-presaging episodic memory decline in individuals at-risk for AD. Apolipoprotein ε4, the highest genetic risk factor for AD, is associated with GABAergic dysfunction in animal models, and episodic memory impairments in humans. In combination, these findings suggest that GABA may be the linchpin in a complex system of factors that eventually leads to the principal clinical hallmark of AD: episodic memory loss. Here, we will review the current state of literature supporting this hypothesis. First, we will focus on the molecular and cellular basis of the GABAergic system and its role in memory and cognition. Next, we report the evidence of GABA dysregulations in AD and normal aging, both in animal models and human studies. Finally, we outline a model of GABAergic dysfunction based on the results of functional neuroimaging studies in humans, which have shown hippocampal hyperactivity to episodic memory tasks concurrent with and even preceding AD diagnosis, along with factors that may modulate this association.

Indexed as

Alzheimer DiseaseAnimalsDisease Models, AnimalGABAergic NeuronsHumansMemory DisordersMiceNeural Networks, ComputerAgingAlzheimer’s diseaseEpisodic memoryHippocampusγ-aminobutyric acid

Identifiers

PMID33573856
PMCPMC8292162
OpenAlexW3126925105

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.