APOLIPOPROTEIN E ε4 ALLELE IMPAIRS CORTICAL ACTIVITY IN HEALTHY AGING AND ALZHEIMER’S DISEASE

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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P2-299: EFFECT OF APOLIPOPROTEIN E ε4 ALLELE ON PROGRESSION RATE OF COGNITIVE DECLINE IN PRODROMAL AND MILD ALZHEIMER'S DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.2706 ◽

2019 ◽

Vol 15 ◽

pp. P701-P701

Author(s):

Kazushi Suzuki ◽

Ryoko Ihara ◽

Takeshi Ikeuchi ◽

Atsushi Iwata ◽

Takeshi Iwatsubo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Apolipoprotein E ◽

Progression Rate ◽

Ε4 Allele

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Effect of apolipoprotein E ε4 allele on the progression of cognitive decline in the early stage of Alzheimer's disease

Alzheimer s & Dementia Translational Research & Clinical Interventions ◽

10.1002/trc2.12007 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Kazushi Suzuki ◽

Akihiro Hirakawa ◽

Ryoko Ihara ◽

Atsushi Iwata ◽

Kenji Ishii ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Apolipoprotein E ◽

Early Stage ◽

Ε4 Allele

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Association of Subjective Hearing Loss and Apolipoprotein E ε4 Allele on Alzheimer's Disease Neurodegeneration

Otology & Neurotology ◽

10.1097/mao.0000000000002855 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Ryan M. Neff ◽

Gregory Jicha ◽

Gregory S. Hawk ◽

Matthew L. Bush ◽

Beth McNulty

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hearing Loss ◽

Apolipoprotein E ◽

Ε4 Allele

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Reduced Hippocampal Insulin-Degrading Enzyme in Late-Onset Alzheimer's Disease Is Associated with the Apolipoprotein E-ε4 Allele

American Journal Of Pathology ◽

10.1016/s0002-9440(10)63822-9 ◽

2003 ◽

Vol 162 (1) ◽

pp. 313-319 ◽

Cited By ~ 213

Author(s):

David G. Cook ◽

James B. Leverenz ◽

Pamela J. McMillan ◽

J. Jacob Kulstad ◽

Sasha Ericksen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Late Onset ◽

Insulin Degrading Enzyme ◽

Degrading Enzyme ◽

Ε4 Allele

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Apolipoprotein E ε4/4 genotype limits response to dietary induction of hyperhomocysteinemia and resulting inflammatory signaling

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211069006 ◽

2022 ◽

pp. 0271678X2110690

Author(s):

Charles E Seaks ◽

Erica M Weekman ◽

Tiffany L Sudduth ◽

Kevin Xie ◽

Brandi Wasek ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Apolipoprotein E ◽

Late Onset ◽

Apoe Ε4 ◽

Perivascular Inflammation ◽

Ε4 Allele ◽

Barrier Breakdown ◽

The Impact

Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind Alzheimer’s disease. Apolipoprotein E (ApoE) is a lipid transporting lipoprotein found within the brain and periphery. The APOE ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease and is a risk factor for VCID. Our lab has previously utilized a dietary model of hyperhomocysteinemia (HHcy) to induce VCID pathology and cognitive deficits in mice. This diet induces perivascular inflammation through cumulative oxidative damage leading to glial mediated inflammation and blood brain barrier breakdown. Here, we examine the impact of ApoE ε4 compared to ε3 alleles on the progression of VCID pathology and inflammation in our dietary model of HHcy. We report a significant resistance to HHcy induction in ε4 mice, accompanied by a number of related differences related to homocysteine (Hcy) metabolism and methylation cycle, or 1-C, metabolites. There were also significant differences in inflammatory profiles between ε3 and ε4 mice, as well as significant reduction in Serpina3n, a serine protease inhibitor associated with ApoE ε4, expression in ε4 HHcy mice relative to ε4 controls. Finally, we find evidence of pervasive sex differences within both genotypes in response to HHcy induction.

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Apolipoprotein E ε4 Allele Frequency and Age at Onset of Alzheimer’s Disease

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000097038 ◽

2006 ◽

Vol 23 (1) ◽

pp. 60-66 ◽

Cited By ~ 35

Author(s):

Yvonne Davidson ◽

Linda Gibbons ◽

Antonia Pritchard ◽

Jayne Hardicre ◽

Joanne Wren ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Allele Frequency ◽

Age At Onset ◽

Ε4 Allele

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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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