Related Experiment Video
Updated: Jun 20, 2026
Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype
Maartje I Kester1, Nicolaas A Verwey, Evert J van Elk
1Alzheimer Center and Department of Neurology, VU University Medical Center Amsterdam, The Netherlands. m.kester@vumc.nl
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.
Insights
Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ42) and tau levels, along with APOE genotype, predict Alzheimer's disease (AD) progression in mild cognitive impairment (MCI). APOE ε4 homozygotes face a very high risk, even with normal Aβ42 levels.
Area of Science:
- Neuroscience
- Biomarker Research
- Genetics
Background:
- Mild cognitive impairment (MCI) is a transitional stage preceding Alzheimer's disease (AD).
- Early prediction of MCI to AD progression is crucial for timely intervention.
- APOE genotype and cerebrospinal fluid (CSF) biomarkers like amyloid-beta 1-42 (Aβ42) and tau are implicated in AD pathogenesis.
Purpose of the Study:
- To investigate the predictive power of CSF Aβ42 and tau levels, in conjunction with APOE genotype, for the progression of MCI to AD.
- To determine if specific APOE genotypes modify the association between CSF biomarkers and AD progression.
Main Methods:
- A cohort of 100 MCI patients underwent CSF Aβ42 and tau level measurements and APOE genotyping.
- Patients were followed for a median of 18 months to assess progression to AD.
- Cox proportional hazards models were employed to analyze the relationships between biomarkers, genotype, and progression.
Main Results:
- An interaction between CSF Aβ42 levels and APOE genotype significantly predicted MCI to AD progression.
- APOE ε4 homozygotes with normal Aβ42 levels exhibited a substantially increased risk of progression (HR: 20.8).
- CSF tau and APOE genotype independently predicted progression to AD.
Conclusions:
- CSF Aβ42 is a stronger predictor of AD progression in APOE ε4 non-carriers.
- APOE ε4 homozygotes demonstrate a markedly elevated risk for AD progression, irrespective of CSF Aβ42 levels.
- Combined assessment of CSF biomarkers and APOE genotype enhances prediction of MCI to AD conversion.
Related Concept Videos
01:29Alzheimer Disease l: Introduction
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
01:23Alzheimer Disease ll: Pathophysiology