Transcriptomics Profiling of Alzheimer’s Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs
Open accessAbstract
The underlying genetic variations of late-onset Alzheimer's disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD pathological process. Transcriptome profiling using deep sequencing technology offers insight into common altered pathways regardless of underpinning genetic or epigenetic factors and thus represents an ideal tool to investigate molecular mechanisms related to the pathophysiology of LOAD. We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of LOAD and age-matched controls. We further validated our data using qRT-PCR on a larger set of postmortem brain tissues, confirming downregulation of the gene encoding substance P (TAC1) and upregulation of the gene encoding the plasminogen activator inhibitor-1 (SERPINE1). Pathway analysis indicates dysregulation in neural communication, cerebral vasculature, and amyloid-β clearance. Beside protein coding genes, we identified several annotated and non-annotated long noncoding RNAs that are differentially expressed in LOAD brain tissues, three of them are activity-dependent regulated and one is induced by Aβ(1-42) exposure of human neural cells. Our data provide a comprehensive list of transcriptomics alterations in LOAD hippocampi and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD.
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Sanchez-Mejias et al. detected higher CD45 gene expression in the hippocampus and parahippocampal gyrus in Alzheimer's disease, whereas Magistri et al. identified no such increase in the hippocampus relative to controls.
“Sanchez-Mejias et al.76 detected higher CD45 gene expression in the hippocampus and parahippocampal gyrus in AD, whereas Magistri et al.71 identified no such increase in the hippocampus relative to controls.”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [71]
Levels of several lncRNAs species are increased in the brain of LOAD patients.
“Levels of several lncRNAs species are increased in the brain of LOAD patients [616].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [616]
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- Authors
- Magistri, M., Velmeshev, D., Makhmutova, M., & Faghihi, M. A.
- Affiliations
- University of Miami (US)
- Corresponding author
- Faghihi, Mohammad Ali
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2015-10-01
- Volume
- 48
- Issue
- 3
- Pages
- 647-665
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC4698155
- OpenAlex
- W2255215236
- Cited by
- 175
- References
- 75
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 17 · 2023: 16 · 2022: 18 · 2021: 23 · 2020: 25 · 2019: 21 · 2018: 24 · 2017: 10 · 2016: 7
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (US NIH NINDS R01NS081208-01A1, R01NS081208)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- late-onset Alzheimer's disease, transcriptomics
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Homeostasis, Humans, Male, Amyloid beta-Peptides, Sequence Analysis, RNA, Gene Expression Profiling, Transcriptome, Real-Time Polymerase Chain Reaction, RNA, Long Noncoding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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