ArticleHuman molecular genetics2014
Human APOE genotype affects intraneuronal Aβ1-42 accumulation in a lentiviral gene transfer model.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- An Insight into Medicinal Chemistry and SAR Studies of Cholinesterase and BACE-1 Inhibitors for Alzheimer's Disease.CNS & neurological disorders drug targets · 2026Review
- Apolipoprotein E intersects with amyloid-β within neurons.Life science alliance · 2023Article
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
- Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE.The Journal of experimental medicine · 2020Article
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease.Molecular neurodegeneration · 2020Review
- Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities.Frontiers in aging neuroscience · 2019Review
- Development of AD-Like Pathology in Skeletal Muscle.Journal of Parkinson's disease and Alzheimer's disease · 2019Article
- The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer's Disease.Frontiers in neuroscience · 2019Article
- Decreased immunoglobulin G in brain regions of elder female APOE4-TR mice accompany with Aβ accumulation.Immunity & ageing : I & A · 2019Article
- The Interplay Between Apolipoprotein E4 and the Autophagic-Endocytic-Lysosomal Axis.Molecular neurobiology · 2018Review
- Apolipoprotein E, Receptors, and Modulation of Alzheimer's Disease.Biological psychiatry · 2018Review
- Blood Markers in Healthy-Aged Nonagenarians: A Combination of High Telomere Length and Low Amyloidβ Are Strongly Associated With Healthy Aging in the Oldest Old.Frontiers in aging neuroscience · 2018Article
- Human Central Nervous System (CNS) ApoE Isoforms Are Increased by Age, Differentially Altered by Amyloidosis, and Relative Amounts Reversed in the CNS Compared with Plasma.The Journal of biological chemistry · 2016Article
- Resveratrol alleviates MPTP-induced motor impairments and pathological changes by autophagic degradation of α-synuclein via SIRT1-deacetylated LC3.Molecular nutrition & food research · 2016Article
- Analyzing dendritic spine pathology in Alzheimer's disease: problems and opportunities.Acta neuropathologica · 2015Review
- APOE Genotype Alters Immunoglobulin Subtypes in Knock-In Mice.Journal of Alzheimer's disease : JAD · 2015Article
- More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration.Neuron · 2014Review
- Dual roles for autophagy: degradation and secretion of Alzheimer's disease Aβ peptide.BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Review
- Molecular basis for increased risk for late-onset Alzheimer disease due to the naturally occurring L28P mutation in apolipoprotein E4.The Journal of biological chemistry · 2014Article
- Aging reduces glial uptake and promotes extracellular accumulation of Aβ from a lentiviral vector.Frontiers in aging neuroscience · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Intraneuronal accumulation of β-amyloid (Aβ)42 is one of the earliest pathological events in humans and in animal models of Alzheimer's disease (AD). Apolipoprotein E 4 (APOE4) is the major identified genetic risk factor for late-onset AD, with Aβ deposition beginning earlier in apoE4-positive subjects. To directly determine the effects of APOE genotype on intraneuronal accumulation of Aβ1-42 at the onset of AD pathogenesis, we introduced lentiviral Aβ1-42 into the cortex of APOE targeted replacement (TR) mice at the age of 8-9 months. We demonstrated a significant isoform-dependent effect of human APOE, with dramatically enhanced intracellular Aβ1-42 deposits in the cerebral cortex of APOE4-TR mice 2 weeks after injection. Double-immunofluorescent staining showed that intracellular accumulation of lentiviral Aβ1-42 was mainly present in neurons, localized to late endosomes/lysosomes. This intraneuronal accumulation of Aβ1-42 correlated with increased tau phosphorylation and cell death in the ipsilateral cortex around the injection site. Aβ1-42 was also observed in microglia, but not in astrocytes. Quantitative analysis revealed more neurons with Aβ1-42 while less microglia with Aβ1-42 nearest to the injection site of Aβ1-42 lentivirus in APOE4-TR mice. Finally, apoE was present in neurons of the ipsilateral cortex of APOE-TR mice at 2 weeks after lentivirus injection, in addition to astrocytes and microglia in both the ipsilateral and contralateral cerebral cortex. Taken together, these results demonstrate that apoE4 tips the balance of the glial and neuronal Aβ toward the intraneuronal accumulation of Aβ.
Indexed as
Identifiers
What OpenQuestion holds
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.