| Autor: |
Quiroz, Yakeel T., Aguillon, David, Zuluaga‐Castaño, Yesica, Baena, Ana Y., Vasquez, Daniel, Garcia, Gloria, Madrigal, Lucia, Hincapie, Liliana, Sanchez, Justin S, Sepulveda‐Falla, Diego, Vila‐Castelar, Clara, Gomez, Liliana Ramirez, Aduen, Paula, Acosta‐Uribe, Juliana, Kosik, Kenneth S., Johnson, Keith A., Sperling, Reisa A., Reiman, Eric M., Lopera, Francisco, Arboleda‐Velasquez, Joseph F |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 12, Vol. 19, p1-2, 2p |
| Abstrakt: |
Background: We previously reported a case of a homozygous woman with the APOE3 Christchurch (R136S, APOE3Ch) variant who demonstrated extreme resistance to autosomal dominant Alzheimer's disease (ADAD) caused by the PSEN1 E280A variant. In this study, we examined the potential protective effects of APOE3Ch against ADAD by characterizing the clinical profile of individuals who were heterozygous for the APOE3Ch variant from the Colombian kindred with the PSEN1 E280A variant. Methods: A total of 421 carriers of the PSEN1 E280A variant were included. Of the 421 carriers, 12 were heterozygous for APOE3Ch (including the previously reported homozygous for APOE3Ch). Clinical and neuropsychological assessments were performed in Spanish at the University of Antioquia in Colombia. Four of the APOE3Ch carriers also donated their brains for postmortem studies. A PSEN1 E280A who is heterozygous for the APOE3Ch variant also underwent structural MRI and amyloid and tau PET imaging. Results: Our findings showed that PSEN1 E280A carriers who are heterozygous carriers of the APOE3Ch variant had a significantly delayed onset for mild cognitive impairment (MCI, median age of 51 vs. 45 years; p = 0.0048) and dementia (52.5 vs. 48 years; p = 0.016), compared to PSEN1 E280A carriers without the APOE3Ch variant. Specifically, APOE3Ch carriers had seven‐time higher odds of developing MCI and three‐time higher odds of developing dementia at a later age than 75% of all the PSEN1 E280A carriers (odds ratio [OR] = 7.6; 95% confidence interval [CI] 1.9, 29.2, p<0.05); dementia OR = 3.07; 95% CI 1.01, 9.33). Initial characterization of brain imaging of a PSEN1 E280A carrier who is heterozygous for the APOE3Ch variant showed levels of medial temporal lobe tau pathology and hippocampal atrophy that were lower than expected for a typical carrier of their age, and similar to our observations in the previously reported APOE3Ch homozygote case. Conclusions: These clinical, cognitive, and neuroimaging data provide evidence that APOE3Ch heterozygosity delays the onset of cognitive decline and may have a protective, dose‐dependent effect against tau pathology and neurodegeneration. These results provide support for the potential of the APOE3Ch variant as a target for the development of new treatments for AD. [ABSTRACT FROM AUTHOR] |
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