The Role of Apolipoprotein E ε4 in Early and Late Mild Cognitive Impairment
Yulin Luo1, Li Tan2, Joseph Therriault3
1Chongqing Three Gorges Medical College, Chongqing, China.
Background:
Apolipoprotein E (APOE) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of APOE ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of APOE ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer's Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ).
Methods:
Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, APOE ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer's disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of APOE ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ-).
Results:
The prevalence of APOE ε4 is higher in EMCI and LMCI than in CN (p < 0.001 for both), and in LMCI than in EMCI (p = 0.001). APOE ε4 allele was significantly higher in Aβ+ subjects than in Aβ- subjects (p < 0.001). Subjects who had a lower CSF Aβ42 level and were APOE ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI.
Conclusions:
An APOE ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that APOE ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.
Insights
The Apolipoprotein E (APOE) ε4 gene variant is linked to worse cognitive function and higher tau levels in early and late mild cognitive impairment (MCI). This association appears to be influenced by amyloid-beta (Aβ) levels.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Apolipoprotein E (APOE) ε4 is strongly associated with mild cognitive impairment (MCI).
- The precise impact of APOE ε4 on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) remains unclear.
- Investigating the role of APOE ε4 in early Alzheimer's disease (AD) progression is crucial.
Purpose of the Study:
- To assess the association between APOE ε4 status, cerebrospinal fluid (CSF) tau levels, and cognitive performance in EMCI and LMCI patients.
- To determine if amyloid-beta (Aβ) levels mediate the relationship between APOE ε4 and tau pathology.
- To utilize data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for comprehensive analysis.
Main Methods:
- Analysis of 269 cognitively normal (CN), 262 EMCI, and 344 LMCI participants from the ADNI database.
- Measurement of CSF Aβ42 and tau levels, APOE ε4 genotyping, and cognitive assessments (MMSE, ADAS-cog).
- Linear regression models were employed to examine associations in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) individuals.
Main Results:
- APOE ε4 prevalence was significantly higher in EMCI and LMCI groups compared to CN, and higher in LMCI than EMCI.
- APOE ε4 allele frequency was greater in Aβ+ subjects than Aβ- subjects.
- Individuals with lower CSF Aβ42 and APOE ε4 positivity exhibited elevated CSF tau and cognitive impairment scores in EMCI/LMCI.
Conclusions:
- APOE ε4 is associated with increased CSF tau and poorer cognition in both EMCI and LMCI.
- Amyloid-beta (Aβ) may mediate the link between APOE ε4 and tau pathology.
- APOE ε4 may play a significant role in mediating tau pathology and cognitive decline during the early stages of AD.
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