Evidence map›Paper›PMID 31771065›Full record

ArticleJournal of Alzheimer's disease : JAD2020

Age-Related Intraneuronal Aggregation of Amyloid-β in Endosomes, Mitochondria, Autophagosomes, and Lysosomes.

Gregory J Brewer, Robert A Herrera, Stephan Philipp, Justyna Sosna, Jorge Mauricio Reyes-Ruiz, Charles G Glabe

Open access · hybridAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Serotonergic Regulation in Alzheimer's Disease.International journal of molecular sciences · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Probing differences among Aβ oligomers with two triangular trimers derived from Aβ.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  19. The Amyloid Cascade Hypothesis 2.0: Generalization of the Concept.Journal of Alzheimer's disease reports · 2023
    Article
  20. Article
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

6 authors at 1 institution in 1 country.

Gregory J BrewerMIND Institute, Center for Neurobiology of Learning and Memory, Irvine, CA, USA.
Robert A HerreraDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.
Stephan PhilippDepartment of Molecular Biology, University of California Irvine, Irvine, CA, USA.
Justyna SosnaDepartment of Molecular Biology, University of California Irvine, Irvine, CA, USA.
Jorge Mauricio Reyes-RuizDepartment of Molecular Biology, University of California Irvine, Irvine, CA, USA.
Charles G GlabeMIND Institute, Center for Neurobiology of Learning and Memory, Irvine, CA, USA.
University of California, Irvine · US

Funding

TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Conformational polymorphisms of amyloid in AD and immunological biomarkers and therapeuticsRF1AG056507 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 2018 to 2019
$3.6M
Endogenous human antibodies in aging and Alzheimer's disease and the immune response to amyloidRF1AG061857 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G., WALSH, CRAIG MICHAEL · 2018 to 2018
$3.5M
Age-related metabolic alterations in amyloid processing in Alzheimer's diseaseRF1AG058218 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BREWER, GREGORY J, GLABE, CHARLES G. · 2018 to 2018
$2.9M
Conformational polymorphisms of amyloid in AD and immunological biomarkers and therapeuticsR56AG056507 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 2017 to 2017
$699k
NIA NIH HHS P01 AG000538NIA NIH HHS R56 AG056507NIA NIH HHS RF1 AG056507NIA NIH HHS RF1 AG058218NIA NIH HHS RF1 AG061857
6 · The paper itself

Abstract

This work provides new insight into the age-related basis of Alzheimer's disease (AD), the composition of intraneuronal amyloid (iAβ), and the mechanism of an age-related increase in iAβ in adult AD-model mouse neurons. A new end-specific antibody for Aβ45 and another for aggregated forms of Aβ provide new insight into the composition of iAβ and the mechanism of accumulation in old adult neurons from the 3xTg-AD model mouse. iAβ levels containing aggregates of Aβ45 increased 30-50-fold in neurons from young to old age and were further stimulated upon glutamate treatment. iAβ was 8 times more abundant in 3xTg-AD than non-transgenic neurons with imaged particle sizes following the same log-log distribution, suggesting a similar snow-ball mechanism of intracellular biogenesis. Pathologically misfolded and mislocalized Alz50 tau colocalized with iAβ and rapidly increased following a brief metabolic stress with glutamate. AβPP-CTF, Aβ45, and aggregated Aβ colocalized most strongly with mitochondria and endosomes and less with lysosomes and autophagosomes. Differences in iAβ by sex were minor. These results suggest that incomplete carboxyl-terminal trimming of long Aβs by gamma-secretase produced large intracellular deposits which limited completion of autophagy in aged neurons. Understanding the mechanism of age-related changes in iAβ processing may lead to application of countermeasures to prolong dementia-free health span.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAutophagosomesCells, CulturedEndosomesGlutamic AcidHumansImmunohistochemistryLysosomesMiceMice, TransgenicMitochondriaNeuronsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorGlutamic AcidAgingAlzheimer’s diseaseamyloidautophagosomesendosomeslysosomesmitochondria

Identifiers

PMID31771065
PMCPMC7029321
OpenAlexW2989971083

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.