Evidence map›Paper›PMID 28988799›Full record

ReviewFree radical biology & medicine2018

Dysfunction of autophagy and endosomal-lysosomal pathways: Roles in pathogenesis of Down syndrome and Alzheimer's Disease.

Daniel J Colacurcio, Anna Pensalfini, Ying Jiang, Ralph A Nixon

Open access · greenAbstract readReview
In one paragraph

Review in Free radical biology & medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 1 pooled it
10.3field-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

102 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.American journal of physiology. Cell physiology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Cyanide overproduction impairs cellular bioenergetics in Down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  9. Article
  10. Interconnections of insulin/IGF-1 signaling and autophagy abnormalities in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

42 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

4 authors at 2 institutions in 1 country.

Daniel J ColacurcioCenter for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA.
Anna PensalfiniCenter for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA.
Ying JiangCenter for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA.
Ralph A NixonCenter for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; Department of Cell Biology, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: Nixon@NKI.RFMH.org.
NYU Langone Health · USNathan Kline Institute for Psychiatric Research · US

Funding

Uncovering Alzheimer's disease risk mechanisms through neuron-specific analysis of autophagy and endosomal-lysosomal functionP01AG017617 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI NIXON, RALPH A. · 2000 to 2021
$40.0M
NIA NIH HHS P01 AG017617
6 · The paper itself

Abstract

Individuals with Down syndrome (DS) have an increased risk of early-onset Alzheimer's Disease (AD), largely owing to a triplication of the APP gene, located on chromosome 21. In DS and AD, defects in endocytosis and lysosomal function appear at the earliest stages of disease development and progress to widespread failure of intraneuronal waste clearance, neuritic dystrophy and neuronal cell death. The same genetic factors that cause or increase AD risk are also direct causes of endosomal-lysosomal dysfunction, underscoring the essential partnership between this dysfunction and APP metabolites in AD pathogenesis. The appearance of APP-dependent endosome anomalies in DS beginning in infancy and evolving into the full range of AD-related endosomal-lysosomal deficits provides a unique opportunity to characterize the earliest pathobiology of AD preceding the classical neuropathological hallmarks. Facilitating this characterization is the authentic recapitulation of this endosomal pathobiology in peripheral cells from people with DS and in trisomy mouse models. Here, we review current research on endocytic-lysosomal dysfunction in DS and AD, the emerging importance of APP/βCTF in initiating this dysfunction, and the potential roles of additional trisomy 21 genes in accelerating endosomal-lysosomal impairment in DS. Collectively, these studies underscore the growing value of investigating DS to probe the biological origins of AD as well as to understand and ameliorate the developmental disability of DS.

Indexed as

AutophagyAlzheimer DiseaseAnimalsDown SyndromeEndosomesHumansLysosomesAlzheimer's DiseaseAutophagyDown syndromeEndosomesLysosomes

Identifiers

PMID28988799
PMCPMC5748263
OpenAlexW2761329528

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.