The apolipoprotein E ϵ4 allele and incident Alzheimer’s disease in persons with mild cognitive impairment

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.

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Gender, apolipoprotein E genotype, and mesial temporal atrophy: 2-year follow-up in patients with stable mild cognitive impairment and with progression from mild cognitive impairment to Alzheimer’s disease

Neuroradiology ◽

10.1007/s00234-016-1740-8 ◽

2016 ◽

Vol 58 (11) ◽

pp. 1143-1151 ◽

Cited By ~ 8

Author(s):

M. V. Spampinato ◽

◽

B. R. Langdon ◽

K. E. Patrick ◽

R. O. Parker ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apolipoprotein E ◽

Apolipoprotein E Genotype

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Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment

European Psychiatry ◽

10.1016/j.eurpsy.2009.02.009 ◽

2010 ◽

Vol 25 (1) ◽

pp. 15-18 ◽

Cited By ~ 9

Author(s):

R. Heun ◽

U. Gühne ◽

T. Luck ◽

M.C. Angermeyer ◽

U. Ueberham ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apolipoprotein E ◽

Target Population ◽

Population Based ◽

Initial Development ◽

Apoe Ε4 ◽

Ε4 Allele

AbstractThe presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) ε4 allele both predict the development of Alzheimer's disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimer's disease. The present study investigates the prevalence of the apoE ε4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183–94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE ε4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p > 0.5). Consequently, the apoE ε4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimer's disease including the initial development of MCI and the later conversion to Alzheimer's disease.

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Is cerebral microbleed prevalence relevant as a biomarker in amnestic mild cognitive impairment and mild Alzheimer’s disease?

The Neuroradiology Journal ◽

10.1177/1971400917720465 ◽

2017 ◽

Vol 30 (5) ◽

pp. 477-485 ◽

Cited By ~ 5

Author(s):

Ana GB Rabelo ◽

Camila VL Teixeira ◽

Thamires NC Magalhães ◽

Ana Flávia MK Carletti-Cassani ◽

Augusto CS Amato Filho ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apolipoprotein E ◽

Tau Protein ◽

Amnestic Mild Cognitive Impairment ◽

Phosphorylated Tau ◽

Phosphorylated Tau Protein ◽

Age And Sex

Introduction The search for a reliable neuroimaging biomarker in Alzheimer’s disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer’s disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer’s disease, amnestic mild cognitive impairment due to Alzheimer’s disease, and normal controls. Moreover, we studied whether microbleeds were associated with apolipoprotein E allele ɛ4 status, cerebrospinal fluid amyloid-beta, total and phosphorylated tau protein levels, vascular factors, and cognition. Methods Twenty-eight mild Alzheimer’s disease patients, 34 with amnestic mild cognitive impairment and 36 cognitively normal elderly subjects underwent: magnetic resonance imaging with a susceptibility-weighted imaging sequence on a 3T scanner, apolipoprotein E genotyping and a full neuropsychological evaluation. Only amnestic mild cognitive impairment and mild Alzheimer’s disease underwent cerebrospinal fluid analysis. We compared the groups and verified if microbleeds were predicted by all other variables. Results Mild Alzheimer’s disease presented a higher prevalence of apolipoprotein E allele ɛ4 in relation to amnestic mild cognitive impairment and control group. No significant differences were found between groups when considering microbleed presence. Logistic regression tests failed to find any relationship between microbleeds and the variables. We performed three different regression models using different independent variables: Model 1 - amyloid-beta, phosphorylated tau protein, total tau, apolipoprotein E allele ɛ4 status, age, and sex; Model 2 - vascular risk factors, age, and sex; Model 3 - cognitive scores sex, age, and education. Conclusion Although microbleeds might be related to the Alzheimer’s disease process, their presence is not a good candidate for a neuroimaging biomarker of the disease, especially in its early phases.

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Apolipoprotein E ε4 and ε3 alleles associate with cerebrospinal fluid tau and cognition in the presence of amyloid-𝜷 in mild cognitive impairment but not in Alzheimer’s disease

Journal of Integrative Neuroscience ◽

10.31083/j.jin2002027 ◽

2021 ◽

Vol 20 (2) ◽

pp. 277

Author(s):

Feng Xing ◽

Tao Meng ◽

Joseph Therriault ◽

Jing Luo ◽

Hua Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apolipoprotein E

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Combining serum and urine biomarkers in the early diagnosis of mild cognitive impairment that evolves into Alzheimer’s disease in patients with the apolipoprotein E ε4 genotype

Biomarkers ◽

10.3109/1354750x.2014.994036 ◽

2014 ◽

Vol 20 (1) ◽

pp. 84-88 ◽

Cited By ~ 19

Author(s):

Chao Wang ◽

Yongjian Cui ◽

Jingci Yang ◽

Jinrong Zhang ◽

Dongcai Yuan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Early Diagnosis ◽

Apolipoprotein E ◽

Urine Biomarkers ◽

Serum And Urine

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Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

Neurodegenerative Diseases ◽

10.1159/000491764 ◽

2018 ◽

Vol 18 (4) ◽

pp. 216-224 ◽

Cited By ~ 4

Author(s):

Anthoula C. Tsolaki ◽

Olympia Gatzima ◽

Makrina Daniilidou ◽

Eutuxia Lazarou ◽

Panagiotis D. Bamidis ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apolipoprotein E ◽

Apoe Genotype ◽

Dependent Manner ◽

Apoe Ε4 ◽

Healthy Elderly ◽

Increased Risk

Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

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