Early energy deficit in Huntington disease : identification of a plasma biomarker traceable during disease progression
Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1)H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2007 |
|---|---|
| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
|---|---|
| Enthalten in: |
PloS one - 2(2007), 7 vom: 25. Juli, Seite e647 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Mochel, Fanny [VerfasserIn] |
|---|
| Themen: |
Amino Acids |
|---|
| Anmerkungen: |
Date Completed 23.04.2010 Date Revised 21.03.2022 published: Electronic Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM171688058 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM171688058 | ||
| 003 | DE-627 | ||
| 005 | 20231223130213.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2007 xx |||||o 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0572.xml |
| 035 | |a (DE-627)NLM171688058 | ||
| 035 | |a (NLM)17653274 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Mochel, Fanny |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Early energy deficit in Huntington disease |b identification of a plasma biomarker traceable during disease progression |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.04.2010 | ||
| 500 | |a Date Revised 21.03.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1)H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Amino Acids |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 700 | 1 | |a Charles, Perrine |e verfasserin |4 aut | |
| 700 | 1 | |a Seguin, François |e verfasserin |4 aut | |
| 700 | 1 | |a Barritault, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Coussieu, Christiane |e verfasserin |4 aut | |
| 700 | 1 | |a Perin, Laurence |e verfasserin |4 aut | |
| 700 | 1 | |a Le Bouc, Yves |e verfasserin |4 aut | |
| 700 | 1 | |a Gervais, Christiane |e verfasserin |4 aut | |
| 700 | 1 | |a Carcelain, Guislaine |e verfasserin |4 aut | |
| 700 | 1 | |a Vassault, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Feingold, Josué |e verfasserin |4 aut | |
| 700 | 1 | |a Rabier, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Durr, Alexandra |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 2(2007), 7 vom: 25. Juli, Seite e647 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:2 |g year:2007 |g number:7 |g day:25 |g month:07 |g pages:e647 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 2 |j 2007 |e 7 |b 25 |c 07 |h e647 | ||