Evidence map›Paper›PMID 26324103›Full record

ArticleMolecular psychiatry2015

Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

M A Lalli, B M Bettcher, M L Arcila, G Garcia, C Guzman, L Madrigal, L Ramirez, J Acosta-Uribe, A Baena, K J Wojta and 11 more

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

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
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  9. Review
  10. Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Article
  11. Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Article
  12. Alteration of Blood Immune Biomarkers in MCI Patients with DifferentInternational journal of molecular sciences · 2023
    Article
  13. Article
  14. Article
  15. Omics-based biomarkers discovery for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2022
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. A novel PSEN2 p.Ser175Phe variant in a family with Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021
    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

21 authors at 6 institutions in 2 countries.

M A LalliNeuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California at Santa Barbara, Santa Barbara, CA, USA.
B M BettcherMemory and Aging Center, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
M L ArcilaNeuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California at Santa Barbara, Santa Barbara, CA, USA.
G GarciaGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
C GuzmanGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
L MadrigalGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
L RamirezGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
J Acosta-UribeGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
A BaenaGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
K J WojtaDepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, USA.
G CoppolaDepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, USA.
R FitchMemory and Aging Center, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
M D de BothNeurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
M J HuentelmanNeurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
E M ReimanNeurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
M E BrunkowInstitute for Systems Biology, Seattle, WA, USA.
G GlusmanInstitute for Systems Biology, Seattle, WA, USA.
J C RoachInstitute for Systems Biology, Seattle, WA, USA.
A W KaoMemory and Aging Center, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
F LoperaGrupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia.
K S KosikNeuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California at Santa Barbara, Santa Barbara, CA, USA.
Universidad de Antioquia · COInstitute for Systems Biology · USUniversity Memory and Aging Center · USTranslational Genomics Research Institute · USUniversity of California, Los Angeles · USUniversity of Arizona · US

Funding

Understanding the molecular functions of progranulin and granulin in FTLDR01NS095257 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAO, AIMEE · 2015 to 2019
$1.9M
Cognitive and Neural Correlates of Inflammation in Healthy Older AdultsK23AG042492 · NIA · UNIVERSITY OF COLORADO DENVER · PI BETTCHER, BRIANNE MAGOUIRK · 2012 to 2016
$716k
NIA NIH HHS K23 AG042492NIA NIH HHS K23 AG042492-01NINDS NIH HHS R01 NS095257
6 · The paper itself

Abstract

We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

Indexed as

AdultAgedAge of OnsetAlzheimer DiseaseChemokine CCL11Chromosomes, Human, Pair 17Cognition DisordersCohort StudiesEnzyme-Linked Immunosorbent AssayFemaleGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideChemokine CCL11

Identifiers

PMID26324103
PMCPMC4759097
OpenAlexW1846129869

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.