Increased expression of cholesterol transporter ABCA1 is highly correlated with severity of dementia in AD hippocampus
Open accessAbstract
To gain insight into ATP-binding cassette transporter A1 (ABCA1) function and its potential role in AD pathology, we analyzed the expression of the cholesterol transporter ABCA1 in postmortem hippocampus from persons at different stages of dementia and AD associated neuropathology relative to cognitively intact normal donors by quantitative polymerase chain reaction (qPCR) and Western blot. In this study clinical dementia rating (CDR) scores were used as a measure of dementia severity, whereas, Braak neuropathological staging and neuritic plaque density were used as an index of the neuropathological progression of AD. Correlation analysis showed that ABCA1 mRNA expression was significantly elevated at the earliest recognizable stage of dementia compared to persons with intact cognition. ABCA1 mRNA was also positively correlated with Braak neuropathological stages and neuritic plaque density counts. Additionally, ABCA1 mRNA levels showed robust correlation with dementia severity even after controlling for the confounding contribution of accompanying neuropathological parameters to ABCA1 mRNA expression. Western blot analyses showed that the differential expression observed at the transcriptional level is also reflected at the protein level. Thus, our study provides transcriptional and translational evidence that the expression of ABCA1, a key modulator of cholesterol transport across the plasma membrane, is dysregulated in the AD brain and that this dysregulation is associated with increasing severity of AD, whether measured functionally as dementia severity or neuropathologically as increased neuritic plaque and neurofibrillary tangle density.
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Levels of ABCA1 highly correlated with severity of cognitive impairment.
“levels of ABCA1 highly correlated with severity of cognitive impairment (Akram et al., 2010).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Akram et al., 2010
ABCA1 expression was increased in the hippocampus of AD cases as well as an AD mouse model.
“Recent studies reported that ABCA1 expression was increased in the hippocampus of AD cases as well as an AD mouse model (Akram et al., 2010; Kim et al., 2010).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Akram et al., 2010
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- Authors
- Akram, A., Schmeidler, J., Katsel, P., Hof, P. R., & Haroutunian, V.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- James J. Peters VA Medical Center (US)
- Corresponding author
- Akram, Afia
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 1318
- Pages
- 167-177
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2826590
- OpenAlex
- W1987562492
- Cited by
- 50
- References
- 96
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 2 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 6
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P01 AG02219, AG05138)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- ABCA1, Alzheimer's disease, dementia severity, hippocampus, cholesterol transport, neuritic plaques, Braak staging, neurofibrillary tangles, gene expression, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Male, Psychiatric Status Rating Scales, RNA, Messenger, Severity of Illness Index, Blotting, Western, Cohort Studies, Polymerase Chain Reaction, ATP-Binding Cassette Transporters, Plaque, Amyloid, ATP Binding Cassette Transporter 1
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