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Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype.
Neurobiol Aging. 2011 Aug; 32(8):1372-8.NA

Abstract

OBJECTIVE

To study CSF biomarkers amyloid-beta 1-42 (Aβ42) and total tau (tau) in relation to APOE genotype in their ability to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).

METHODS

In 100 MCI patients CSF Aβ42, tau and APOE genotype were determined. At follow-up of 18 (13-24) months 58 patients remained non-progressive and 42 progressed to AD.

RESULTS

Cox proportional hazards models showed an interaction between Aβ42 and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for abnormal Aβ42 of 8.2 (2.1-31.9) for ε4 non-carriers, 3.9 (0.8-18.5) for heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for Aβ42 revealed that in patients with normal levels of Aβ42, ε4 homozygotes had a strongly increased risk of progression to AD with HR (95% CI) 20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD.

CONCLUSIONS

Aβ42 was a stronger predictor of progression to AD in APOE ε4 non-carriers than in carriers. Furthermore, the risk of progression for ε4 homozygotes was very high, also in patients with normal levels of Aβ42.

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Authors+Show Affiliations

Kester MI
Alzheimer Center and Department of Neurology, VU University Medical Center Amsterdam, The Netherlands. m.kester@vumc.nl
Verwey NA
No affiliation info available
van Elk EJ
No affiliation info available
Blankenstein MA
No affiliation info available
Scheltens P
No affiliation info available
van der Flier WM
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4Cognitive DysfunctionDisease ProgressionFemaleGenetic Carrier ScreeningGenotypeHomozygoteHumansMaleMiddle AgedPeptide FragmentsPredictive Value of TestsSeverity of Illness Index

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19748159

Citation

Kester, Maartje I., et al. "Progression From MCI to AD: Predictive Value of CSF Aβ42 Is Modified By APOE Genotype." Neurobiology of Aging, vol. 32, no. 8, 2011, pp. 1372-8.
Kester MI, Verwey NA, van Elk EJ, et al. Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype. Neurobiol Aging. 2011;32(8):1372-8.
Kester, M. I., Verwey, N. A., van Elk, E. J., Blankenstein, M. A., Scheltens, P., & van der Flier, W. M. (2011). Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype. Neurobiology of Aging, 32(8), 1372-8. https://doi.org/10.1016/j.neurobiolaging.2009.08.006
Kester MI, et al. Progression From MCI to AD: Predictive Value of CSF Aβ42 Is Modified By APOE Genotype. Neurobiol Aging. 2011;32(8):1372-8. PubMed PMID: 19748159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype. AU - Kester,Maartje I, AU - Verwey,Nicolaas A, AU - van Elk,Evert J, AU - Blankenstein,Marinus A, AU - Scheltens,Philip, AU - van der Flier,Wiesje M, Y1 - 2009/09/11/ PY - 2009/01/30/received PY - 2009/07/21/revised PY - 2009/08/17/accepted PY - 2009/9/15/entrez PY - 2009/9/15/pubmed PY - 2012/5/15/medline SP - 1372 EP - 8 JF - Neurobiology of aging JO - Neurobiol Aging VL - 32 IS - 8 N2 - OBJECTIVE: To study CSF biomarkers amyloid-beta 1-42 (Aβ42) and total tau (tau) in relation to APOE genotype in their ability to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In 100 MCI patients CSF Aβ42, tau and APOE genotype were determined. At follow-up of 18 (13-24) months 58 patients remained non-progressive and 42 progressed to AD. RESULTS: Cox proportional hazards models showed an interaction between Aβ42 and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for abnormal Aβ42 of 8.2 (2.1-31.9) for ε4 non-carriers, 3.9 (0.8-18.5) for heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for Aβ42 revealed that in patients with normal levels of Aβ42, ε4 homozygotes had a strongly increased risk of progression to AD with HR (95% CI) 20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD. CONCLUSIONS: Aβ42 was a stronger predictor of progression to AD in APOE ε4 non-carriers than in carriers. Furthermore, the risk of progression for ε4 homozygotes was very high, also in patients with normal levels of Aβ42. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/19748159/Progression_from_MCI_to_AD:_predictive_value_of_CSF_Aβ42_is_modified_by_APOE_genotype_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(09)00266-8 DB - PRIME DP - Unbound Medicine ER -