Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients
Alzheimer’s disease (AD) is the most common form of dementia in the elderly and has been associated with changes in lipoprotein metabolism. We performed quantitative lipoprotein analysis in a local cohort of cognitively impaired elderly and control subjects using standardized nuclear magnetic resona...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12472 |
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| author | Georgy Berezhnoy Christoph Laske Christoph Trautwein |
| author_facet | Georgy Berezhnoy Christoph Laske Christoph Trautwein |
| author_sort | Georgy Berezhnoy |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common form of dementia in the elderly and has been associated with changes in lipoprotein metabolism. We performed quantitative lipoprotein analysis in a local cohort of cognitively impaired elderly and control subjects using standardized nuclear magnetic resonance (NMR) spectroscopy. A commercially available quantitative NMR-based assay covering 112 lipoprotein main and subtype variables was used to investigate blood serum samples from a moderate cohort size of 161 persons (71 female, 90 male), including measures of quality control. Additionally, clinical metadata and cerebrospinal fluid AD biomarkers were collected and used for analysis. High-density lipoprotein (HDL) HDL-4 subfraction levels were mostly high in female individuals with mild cognitive impairment (MCI), followed by AD. Low-density lipoprotein (LDL) LDL-2 cholesterol was slightly elevated in male AD patients. HDL-2 apolipoprotein Apo-A1, HDL-2 phospholipids, and HDL-3 triglycerides were highly abundant in AD and MCI women compared to men. When considering clinical biomarkers (Aβ, tau), very low-density lipoprotein (VLDL) VLDL-1 and intermediate-density lipoprotein (IDL) triglycerides were substantially higher in AD compared to MCI. In addition, triglyceride levels correlated positively with dementia. Different lipoprotein serum patterns were identified for AD, MCI, and control subjects. Interestingly, HDL-4 and LDL-2 cholesterol parameters revealed strong gender-specific changes in the context of AD-driven dementia. As gender-based comparisons were based on smaller sub-groups with a low n-number, several statistical findings did not meet the significance threshold for multiple comparisons testing. Still, our finding suggests that serum HDL-4 parameters and various triglycerides correlate positively with AD pathology which could be a read-out of extended lipids traveling through the blood-brain barrier, supporting amyloid plaque formation processes. Thereof, we see herein a proof of concept that this quantitative NMR-based lipoprotein assay can generate important and highly interesting data for refined AD diagnosis and patient stratification, especially when larger cohorts are available. |
| first_indexed | 2024-03-09T20:05:36Z |
| format | Article |
| id | doaj.art-30fa592542fc48868132d47750372bd5 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:05:36Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-30fa592542fc48868132d47750372bd52023-11-24T00:32:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201247210.3390/ijms232012472Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease PatientsGeorgy Berezhnoy0Christoph Laske1Christoph Trautwein2Laboratory for Metabolomics and Systems Medicine, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, 72076 Tübingen, GermanySection for Dementia Research, Hertie Institute for Clinical Brain Research, Department of Psychiatry and Psychotherapy, University Hospital Tübingen, 72076 Tübingen, GermanyLaboratory for Metabolomics and Systems Medicine, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, 72076 Tübingen, GermanyAlzheimer’s disease (AD) is the most common form of dementia in the elderly and has been associated with changes in lipoprotein metabolism. We performed quantitative lipoprotein analysis in a local cohort of cognitively impaired elderly and control subjects using standardized nuclear magnetic resonance (NMR) spectroscopy. A commercially available quantitative NMR-based assay covering 112 lipoprotein main and subtype variables was used to investigate blood serum samples from a moderate cohort size of 161 persons (71 female, 90 male), including measures of quality control. Additionally, clinical metadata and cerebrospinal fluid AD biomarkers were collected and used for analysis. High-density lipoprotein (HDL) HDL-4 subfraction levels were mostly high in female individuals with mild cognitive impairment (MCI), followed by AD. Low-density lipoprotein (LDL) LDL-2 cholesterol was slightly elevated in male AD patients. HDL-2 apolipoprotein Apo-A1, HDL-2 phospholipids, and HDL-3 triglycerides were highly abundant in AD and MCI women compared to men. When considering clinical biomarkers (Aβ, tau), very low-density lipoprotein (VLDL) VLDL-1 and intermediate-density lipoprotein (IDL) triglycerides were substantially higher in AD compared to MCI. In addition, triglyceride levels correlated positively with dementia. Different lipoprotein serum patterns were identified for AD, MCI, and control subjects. Interestingly, HDL-4 and LDL-2 cholesterol parameters revealed strong gender-specific changes in the context of AD-driven dementia. As gender-based comparisons were based on smaller sub-groups with a low n-number, several statistical findings did not meet the significance threshold for multiple comparisons testing. Still, our finding suggests that serum HDL-4 parameters and various triglycerides correlate positively with AD pathology which could be a read-out of extended lipids traveling through the blood-brain barrier, supporting amyloid plaque formation processes. Thereof, we see herein a proof of concept that this quantitative NMR-based lipoprotein assay can generate important and highly interesting data for refined AD diagnosis and patient stratification, especially when larger cohorts are available.https://www.mdpi.com/1422-0067/23/20/12472<sup>1</sup>H-NMRserumlipoproteinsliquorbeta-amyloidtau |
| spellingShingle | Georgy Berezhnoy Christoph Laske Christoph Trautwein Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients International Journal of Molecular Sciences <sup>1</sup>H-NMR serum lipoproteins liquor beta-amyloid tau |
| title | Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients |
| title_full | Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients |
| title_fullStr | Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients |
| title_full_unstemmed | Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients |
| title_short | Quantitative NMR-Based Lipoprotein Analysis Identifies Elevated HDL-4 and Triglycerides in the Serum of Alzheimer’s Disease Patients |
| title_sort | quantitative nmr based lipoprotein analysis identifies elevated hdl 4 and triglycerides in the serum of alzheimer s disease patients |
| topic | <sup>1</sup>H-NMR serum lipoproteins liquor beta-amyloid tau |
| url | https://www.mdpi.com/1422-0067/23/20/12472 |
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