Evidence map›Paper›PMID 34708251›Full record

ReviewCellular and molecular life sciences : CMLS2021

Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.

Yihan Li, Simon M Laws, Luke A Miles, James S Wiley, Xin Huang, Colin L Masters, Ben J Gu

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

Review in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

51 citing papers in PubMed, 88 citations in OpenAlex.

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  10. MAVISp: A modular structure-based framework for protein variant effects.Protein science : a publication of the Protein Society · 2026
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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

7 authors at 2 institutions in 1 country.

Yihan LiThe Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0002-5784-3717
Simon M LawsCentre for Precision Health, Edith Cowan University, 270 Joondalup Dr, Joondalup, WA, 6027, Australia.
Luke A MilesThe Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
James S WileyThe Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
Xin HuangThe Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
Colin L MastersThe Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
Ben J GuThe Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia. ben.gu@florey.edu.au.
The University of Melbourne · AUEdith Cowan University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterised by cognitive impairment, behavioural alteration, and functional decline. Over 130 AD-associated susceptibility loci have been identified by genome-wide association studies (GWAS), while whole genome sequencing (WGS) and whole exome sequencing (WES) studies have identified AD-associated rare variants. These variants are enriched in APOE, TREM2, CR1, CD33, CLU, BIN1, CD2AP, PILRA, SCIMP, PICALM, SORL1, SPI1, RIN3, and more genes. Given that aging is the single largest risk factor for late-onset AD (LOAD), the accumulation of somatic mutations in the brain and blood of AD patients have also been explored. Collectively, these genetic findings implicate the role of innate and adaptive immunity in LOAD pathogenesis and suggest that a systemic failure of cell-mediated amyloid-β (Aβ) clearance contributes to AD onset and progression. AD-associated variants are particularly enriched in myeloid-specific regulatory regions, implying that AD risk variants are likely to perturbate the expression of myeloid-specific AD-associated genes to interfere Aβ clearance. Defective phagocytosis, endocytosis, and autophagy may drive Aβ accumulation, which may be related to naturally-occurring antibodies to Aβ (Nabs-Aβ) produced by adaptive responses. Passive immunisation is providing efficiency in clearing Aβ and slowing cognitive decline, such as aducanumab, donanemab, and lecanemab (ban2401). Causation of AD by impairment of the innate immunity and treatment using the tools of adaptive immunity is emerging as a new paradigm for AD, but immunotherapy that boosts the innate immune functions of myeloid cells is highly expected to modulate disease progression at asymptomatic stage.

Indexed as

Adaptive ImmunityAgingAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedAntigen PresentationAutophagyGenome-Wide Association StudyHumansImmunity, InnatePolymorphism, Single NucleotideaducanumabAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedlecanemabAmyloid plaquesEndo-lysosomal networkMicrogliaMonocytesNeurodegenerationPolygenic risk scoreSingle nucleotide polymorphism

Identifiers

PMID34708251
PMCPMC11073066
OpenAlexW3208670486

What Socratic holds

Textmetadata
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.