ArticleJournal of neuropathology and experimental neurology2021
Inflammatory Pathways Are Impaired in Alzheimer Disease and Differentially Associated With Apolipoprotein E Status.
Article in Journal of neuropathology and experimental neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Pooled it
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages.Annals of clinical and translational neurology · 2026Article
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Similar Normalizing Effect of HSP70 and YB-1 Stress Proteins on the Brain Transcription of a Mouse Model of Alzheimer's Disease.Molecular neurobiology · 2025Article
- APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.Neurobiology of disease · 2025Article
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- Sex/gender effects of glial reactivity on preclinical Alzheimer's disease pathology.Molecular psychiatry · 2025Article
- Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Review
- APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward Aβ, through P2RY12.Molecular neurodegeneration · 2024Article
- Three major effects of APOEFrontiers in aging neuroscience · 2024Review
- Association between APOE genotype and microglial cell morphology.Journal of neuropathology and experimental neurology · 2023Article
- APOE and immunity: Research highlights.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Neuropathology-Independent Association BetweenNeurology. Genetics · 2023Article
- Cellular senescence in brain aging and cognitive decline.Frontiers in aging neuroscience · 2023Review
- Shared genetic architecture of COVID-19 and Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination.Molecular neurodegeneration · 2022Article
- Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process.International journal of molecular sciences · 2022Review
- Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.Free neuropathology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer disease (AD) is a neurodegenerative disease characterized by a cognitive decline leading to dementia. The most impactful genetic risk factor is apolipoprotein E (APOE). APOE-ε4 significantly increases AD risk, APOE-ε3 is the most common gene variant, and APOE-ε2 protects against AD. However, the underlying mechanisms of APOE-ε4 on AD risk remains unclear, with APOE-ε4 impacting many pathways. We investigated how the APOE isoforms associated with the neuroinflammatory state of the brain with and without AD pathology. Frozen brain tissue from the superior and middle temporal gyrus was analyzed from APOE-ε3/3 (n = 9) or APOE-ε4/4 (n = 10) participants with AD pathology and APOE-ε3/3 (n = 9) participants without AD pathology. We determined transcript levels of 757 inflammatory related genes using the NanoString Human Neuroinflammation Panel. We found significant pathways impaired in APOE-ε4/4-AD individuals compared to APOE-ε3/3-AD. Of interest, expression of genes related to microglial activation (SALL1), motility (FSCN1), epigenetics (DNMT1), and others showed altered expression. Additionally, we performed immunohistochemistry of P2RY12 to confirm reduced microglial activation. Our results suggest APOE-ε3 responds to AD pathology while potentially having a harmful long-term inflammatory response, while APOE-ε4 shows a weakened response to pathology. Overall, APOE isoforms appear to modulate the brain immune response to AD-type pathology.
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Registered trials
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.