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Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease.
Arch Neurol 2007; 64(3):354-62AN

Abstract

BACKGROUND

To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease.

OBJECTIVE

To determine whether plasma levels of amyloid beta protein (Abeta40 and Abeta42) are useful for identifying cognitively normal elderly white subjects at increased risk for mild cognitive impairment (MCI) and AD.

DESIGN

Using well-established sandwich enzyme-linked immunosorbent assays, plasma Abeta40 and Abeta42 levels were analyzed at baseline in a prospective, elderly white cohort followed up for 2 to 12 (median, 3.7) years to detect incident cases of MCI or AD.

SETTING

Cognitively normal, community-based white volunteers recruited from primary care settings into the Mayo Rochester Alzheimer Disease Patient Registry. Patients We followed up 563 cognitively normal white volunteers (median age, 78 years; 62% female) who had at least 1 follow-up visit after measurement of baseline plasma Abeta levels.

MAIN OUTCOME MEASURES

The primary outcome was time to development of MCI or AD. The secondary outcome was the annualized rate of cognitive change in patients for whom we had 2 Mattis Dementia Rating Scale evaluations 3 to 7 years apart.

RESULTS

During follow-up, 53 subjects developed MCI or AD. Subjects with plasma Abeta42/Abeta40 ratios in the lower quartiles showed significantly greater risk of MCI or AD (P = .04, adjusted for age and apolipoprotein E genotype). Comparison of subjects with plasma Abeta42/Abeta40 ratios in the lowest vs the highest quartile gave a relative risk of 3.1 (95% confidence interval, 1.1-8.3). After adjusting for age and apolipoprotein E genotype, regression analysis using annualized changes in the Dementia Rating Scale scores as an outcome variable showed that participants with lower Abeta42/Abeta40 ratios had greater cognitive decline (P = .02).

CONCLUSION

The plasma Abeta42/Abeta40 ratio may be a useful premorbid biomarker for identifying cognitively normal elderly white subjects who are at increased risk for developing MCI or AD.

Authors+Show Affiliations

Department of Neuroscience, Mayo College of Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA. graffradford.neill@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17353377

Citation

Graff-Radford, Neill R., et al. "Association of Low Plasma Abeta42/Abeta40 Ratios With Increased Imminent Risk for Mild Cognitive Impairment and Alzheimer Disease." Archives of Neurology, vol. 64, no. 3, 2007, pp. 354-62.
Graff-Radford NR, Crook JE, Lucas J, et al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol. 2007;64(3):354-62.
Graff-Radford, N. R., Crook, J. E., Lucas, J., Boeve, B. F., Knopman, D. S., Ivnik, R. J., ... Younkin, S. G. (2007). Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Archives of Neurology, 64(3), pp. 354-62.
Graff-Radford NR, et al. Association of Low Plasma Abeta42/Abeta40 Ratios With Increased Imminent Risk for Mild Cognitive Impairment and Alzheimer Disease. Arch Neurol. 2007;64(3):354-62. PubMed PMID: 17353377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. AU - Graff-Radford,Neill R, AU - Crook,Julia E, AU - Lucas,John, AU - Boeve,Bradley F, AU - Knopman,David S, AU - Ivnik,Robert J, AU - Smith,Glenn E, AU - Younkin,Linda H, AU - Petersen,Ronald C, AU - Younkin,Steven G, PY - 2007/3/14/pubmed PY - 2007/4/25/medline PY - 2007/3/14/entrez SP - 354 EP - 62 JF - Archives of neurology JO - Arch. Neurol. VL - 64 IS - 3 N2 - BACKGROUND: To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease. OBJECTIVE: To determine whether plasma levels of amyloid beta protein (Abeta40 and Abeta42) are useful for identifying cognitively normal elderly white subjects at increased risk for mild cognitive impairment (MCI) and AD. DESIGN: Using well-established sandwich enzyme-linked immunosorbent assays, plasma Abeta40 and Abeta42 levels were analyzed at baseline in a prospective, elderly white cohort followed up for 2 to 12 (median, 3.7) years to detect incident cases of MCI or AD. SETTING: Cognitively normal, community-based white volunteers recruited from primary care settings into the Mayo Rochester Alzheimer Disease Patient Registry. Patients We followed up 563 cognitively normal white volunteers (median age, 78 years; 62% female) who had at least 1 follow-up visit after measurement of baseline plasma Abeta levels. MAIN OUTCOME MEASURES: The primary outcome was time to development of MCI or AD. The secondary outcome was the annualized rate of cognitive change in patients for whom we had 2 Mattis Dementia Rating Scale evaluations 3 to 7 years apart. RESULTS: During follow-up, 53 subjects developed MCI or AD. Subjects with plasma Abeta42/Abeta40 ratios in the lower quartiles showed significantly greater risk of MCI or AD (P = .04, adjusted for age and apolipoprotein E genotype). Comparison of subjects with plasma Abeta42/Abeta40 ratios in the lowest vs the highest quartile gave a relative risk of 3.1 (95% confidence interval, 1.1-8.3). After adjusting for age and apolipoprotein E genotype, regression analysis using annualized changes in the Dementia Rating Scale scores as an outcome variable showed that participants with lower Abeta42/Abeta40 ratios had greater cognitive decline (P = .02). CONCLUSION: The plasma Abeta42/Abeta40 ratio may be a useful premorbid biomarker for identifying cognitively normal elderly white subjects who are at increased risk for developing MCI or AD. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/17353377/Association_of_low_plasma_Abeta42/Abeta40_ratios_with_increased_imminent_risk_for_mild_cognitive_impairment_and_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.64.3.354 DB - PRIME DP - Unbound Medicine ER -