Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease.
The combination of decreased amyloid β42 (Aβ42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer’s disease (AD). Previous studies showed significant heterogeneity in CSF...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fneur.2015.00247/full |
| _version_ | 1828405582045904896 |
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| author | Aline eDorey Aline eDorey Armand ePerret-Liaudet Armand ePerret-Liaudet Armand ePerret-Liaudet Yannick eTholance Yannick eTholance Anthony eFourier Anthony eFourier Isabelle eQuadrio Isabelle eQuadrio |
| author_facet | Aline eDorey Aline eDorey Armand ePerret-Liaudet Armand ePerret-Liaudet Armand ePerret-Liaudet Yannick eTholance Yannick eTholance Anthony eFourier Anthony eFourier Isabelle eQuadrio Isabelle eQuadrio |
| author_sort | Aline eDorey |
| collection | DOAJ |
| description | The combination of decreased amyloid β42 (Aβ42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer’s disease (AD). Previous studies showed significant heterogeneity in CSF Aβ42 levels to discriminate AD from non-AD patients. It was also suggested that the CSF amyloid peptide β42/β40 ratio has better diagnostic performance than Aβ42 alone. The objective of the present study was to investigate the potential added value of determining CSF amyloid β40 peptide (Aβ40) for biological diagnosis of AD when CSF Aβ42 levels failed.CSF AD biomarkers were run in 2,171 samples from 1,499 AD and 672 non-AD patients. The following pathologic thresholds were used to define an AD-positive CSF biomarker profile: T-Tau ≥ 400 ng/L, P-Tau181 ≥ 60 ng/L and Aβ42 ≤ 700 ng/L. CSF Aβ40 was assayed in AD patients with CSF Aβ42 levels above 700 ng/L and non-AD patients with CSF Aβ42 levels below 700 ng/L. CSF Aβ40 levels were higher in AD than non-AD patients. The ROC curves of CSF Aβ40 and the Aβ42/Aβ40 ratio defined AD cut off values at 12,644 ng/L and 0.06 respectively. In AD patients with non-pathological CSF Aβ42, CSF Aβ40 concentration was able to correct 76.2% of cases when expressed as CSF Aβ42/Aβ40 ratio and 94.7% of cases when used alone. Using CSF Aβ42 and then CSF Aβ40, the percentage of misinterpreted AD patients fell to 1.0%.CSF Aβ40 concentration improved interpretation of Aβ42 level for the diagnosis of Alzheimer’s disease. CSF Aβ40 alone showed better diagnostic performance than the amyloid peptide Aβ42/Aβ40 ratio. The added value of determining CSF Aβ40 in AD diagnosis now needs confirming in a cohort of definite AD patients and to be completed with novel amyloid cascade biomarkers. |
| first_indexed | 2024-12-10T10:56:00Z |
| format | Article |
| id | doaj.art-74eed61445b845c4b8a91ad83d9d903b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-10T10:56:00Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-74eed61445b845c4b8a91ad83d9d903b2022-12-22T01:51:52ZengFrontiers Media S.A.Frontiers in Neurology1664-22952015-11-01610.3389/fneur.2015.00247152684Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease.Aline eDorey0Aline eDorey1Armand ePerret-Liaudet2Armand ePerret-Liaudet3Armand ePerret-Liaudet4Yannick eTholance5Yannick eTholance6Anthony eFourier7Anthony eFourier8Isabelle eQuadrio9Isabelle eQuadrio10Hospices Civils de LyonHospices Civils de Lyon, Lyon1 UniversityHospices Civils de LyonINSERMHospices Civils de Lyon, Lyon1 UniversityHospices Civils de LyonCentre Hospitalier Universitaire de LimogesHospices Civils de LyonINSERMHospices Civils de LyonINSERMThe combination of decreased amyloid β42 (Aβ42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer’s disease (AD). Previous studies showed significant heterogeneity in CSF Aβ42 levels to discriminate AD from non-AD patients. It was also suggested that the CSF amyloid peptide β42/β40 ratio has better diagnostic performance than Aβ42 alone. The objective of the present study was to investigate the potential added value of determining CSF amyloid β40 peptide (Aβ40) for biological diagnosis of AD when CSF Aβ42 levels failed.CSF AD biomarkers were run in 2,171 samples from 1,499 AD and 672 non-AD patients. The following pathologic thresholds were used to define an AD-positive CSF biomarker profile: T-Tau ≥ 400 ng/L, P-Tau181 ≥ 60 ng/L and Aβ42 ≤ 700 ng/L. CSF Aβ40 was assayed in AD patients with CSF Aβ42 levels above 700 ng/L and non-AD patients with CSF Aβ42 levels below 700 ng/L. CSF Aβ40 levels were higher in AD than non-AD patients. The ROC curves of CSF Aβ40 and the Aβ42/Aβ40 ratio defined AD cut off values at 12,644 ng/L and 0.06 respectively. In AD patients with non-pathological CSF Aβ42, CSF Aβ40 concentration was able to correct 76.2% of cases when expressed as CSF Aβ42/Aβ40 ratio and 94.7% of cases when used alone. Using CSF Aβ42 and then CSF Aβ40, the percentage of misinterpreted AD patients fell to 1.0%.CSF Aβ40 concentration improved interpretation of Aβ42 level for the diagnosis of Alzheimer’s disease. CSF Aβ40 alone showed better diagnostic performance than the amyloid peptide Aβ42/Aβ40 ratio. The added value of determining CSF Aβ40 in AD diagnosis now needs confirming in a cohort of definite AD patients and to be completed with novel amyloid cascade biomarkers.http://journal.frontiersin.org/Journal/10.3389/fneur.2015.00247/fullCerebrospinal FluidDementiaAlzheimerAβ42Aβ40 |
| spellingShingle | Aline eDorey Aline eDorey Armand ePerret-Liaudet Armand ePerret-Liaudet Armand ePerret-Liaudet Yannick eTholance Yannick eTholance Anthony eFourier Anthony eFourier Isabelle eQuadrio Isabelle eQuadrio Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. Frontiers in Neurology Cerebrospinal Fluid Dementia Alzheimer Aβ42 Aβ40 |
| title | Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. |
| title_full | Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. |
| title_fullStr | Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. |
| title_full_unstemmed | Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. |
| title_short | Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. |
| title_sort | cerebrospinal fluid aβ40 improves the interpretation of aβ42 concentration for diagnosing alzheimer s disease |
| topic | Cerebrospinal Fluid Dementia Alzheimer Aβ42 Aβ40 |
| url | http://journal.frontiersin.org/Journal/10.3389/fneur.2015.00247/full |
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