P2-299: EFFECT OF APOLIPOPROTEIN E ε4 ALLELE ON PROGRESSION RATE OF COGNITIVE DECLINE IN PRODROMAL AND MILD 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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Apolipoprotein E and cognitive decline in Alzheimer's disease

Neurology ◽

10.1212/wnl.47.2.317 ◽

1996 ◽

Vol 47 (2) ◽

pp. 317-320 ◽

Cited By ~ 20

Author(s):

B. L. Plassman ◽

J. C.S. Breitner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Apolipoprotein E

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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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A-5 Examining the Interactive Effects of Traumatic Brain Injury and Apolipoprotein E on Cognitive Decline in Alzheimer’s Disease

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.23 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1044-1044

Author(s):

Claire Alexander ◽

Julie Suhr

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Apolipoprotein E ◽

Negative Impact ◽

Interactive Effects ◽

Decline Rate ◽

History Of ◽

Positive Effect

Abstract Objective Little research has focused on possible effects of TBI on cognitive decline rate after Alzheimer’s disease (ad) diagnosis. We examined whether Apolipoprotein E (APOE) status and TBI history interact to predict cognitive decline. Method We used data from the National Alzheimer’s Coordinating Centers (N = 463; 42.3% APOE e4 carriers, 7.8% with TBI history, mean baseline age 79.3). Inclusion criteria included normal cognition at baseline with diagnosis of ad at a follow-up visit; baseline age 50 or older; and at least 3 years of follow-up data. Mixed models (random intercept, random slope) were used, with TBI history, APOE status, and their interaction as predictors of interest. Education, race, and history of TIA, stroke, or hypertension were included as covariates. Cognitive measures included mental status exam scores and immediate/delayed story memory. Results After accounting for covariates, TBI history had a positive effect on cognitive decline rate on the screener and immediate memory measures. APOE status did not affect rate of cognitive decline on the screener, but presence of e4 predicted faster decline on immediate and delayed memory. TBI history and APOE status interacted to predict delayed memory decline, such that history of TBI was associated with a reduced rate of decline for e4 non-carriers but there was no effect of TBI for e4 carriers. Conclusion When examining cognitive decline trajectory, TBI history predicted slower decline (a positive effect) while APOE had either a negative impact or no effect, depending on the measure. Future study should examine cognitive decline in the context of demographic and genetic factors.

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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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