Severe COVID-19 in Alzheimer's Disease: APOE4's Fault Again?

Overview

Journal Alzheimers Res Ther

Date 2021 Jun 13

PMID 34118974

Citations 26

Authors

Nian Xiong

Martin R Schiller

Jingwen Li

Xiaowu Chen

Zhicheng Lin

Affiliations

Soon will be listed here.

Abstract

Challenges have been recognized in healthcare of patients with Alzheimer's disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE with COVID-19 risk factors such as ACE2, TMPRSS2, NRP1, and LZTFL1; at a behavioral level, APOE4-associated dementia may increase the exposure to coronavirus infection which causes COVID-19. Thus, APOE4 could exert multiple actions for high infection and mortality rates of the patients, or generally, with COVID-19.

Citing Articles

Anti-Inflammatory and Neuroprotective Polyphenols Derived from the European Olive Tree, L., in Long COVID and Other Conditions Involving Cognitive Impairment.

Papadopoulou P, Polissidis A, Kythreoti G, Sagnou M, Stefanatou A, Theoharides T Int J Mol Sci. 2024; 25(20).

PMID: 39456822 PMC: 11507169. DOI: 10.3390/ijms252011040.

Impact of COVID-19 pandemic on mortality rate in memory clinic patients.

Bakker E, van Maurik I, Zwan M, Gillissen F, van der Veere P, Bouwman F Alzheimers Dement (Amst). 2024; 16(1):e12541.

PMID: 38288266 PMC: 10823153. DOI: 10.1002/dad2.12541.

Alzheimer's Disease and Cancer: Common Targets.

Yang X, Dai J, Wu C, Liu Z Mini Rev Med Chem. 2023; 24(10):983-1000.

PMID: 38037912 DOI: 10.2174/0113895575263108231031132404.

COVID-19 and Alzheimer's Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future.

Amadoro G, Latina V, Stigliano E, Micera A Cells. 2023; 12(22).

PMID: 37998336 PMC: 10670749. DOI: 10.3390/cells12222601.

Shared genetic architecture of COVID-19 and Alzheimer's disease.

Matveeva N, Kiselev I, Baulina N, Semina E, Kakotkin V, Agapov M Front Aging Neurosci. 2023; 15:1287322.

PMID: 37927339 PMC: 10625425. DOI: 10.3389/fnagi.2023.1287322.

References

Brai E, Alina Raio N, Alberi L . Notch1 hallmarks fibrillary depositions in sporadic Alzheimer's disease. Acta Neuropathol Commun. 2016; 4(1):64. PMC: 4929714. DOI: 10.1186/s40478-016-0327-2. View

Van Gool B, Storck S, Reekmans S, Lechat B, Gordts P, Pradier L . LRP1 Has a Predominant Role in Production over Clearance of Aβ in a Mouse Model of Alzheimer's Disease. Mol Neurobiol. 2019; 56(10):7234-7245. PMC: 6728278. DOI: 10.1007/s12035-019-1594-2. View

Zhang Z, Li X, Wang Z, Song M, Yu S, Kang S . δ-Secretase-cleaved Tau stimulates Aβ production via upregulating STAT1-BACE1 signaling in Alzheimer's disease. Mol Psychiatry. 2018; 26(2):586-603. PMC: 6684859. DOI: 10.1038/s41380-018-0286-z. View

Lim K, Yang S, Kim S, Joo J . Identifying New COVID-19 Receptor Neuropilin-1 in Severe Alzheimer's Disease Patients Group Brain Using Genome-Wide Association Study Approach. Front Genet. 2021; 12:741175. PMC: 8566993. DOI: 10.3389/fgene.2021.741175. View

Michaelson D . APOE ε4: the most prevalent yet understudied risk factor for Alzheimer's disease. Alzheimers Dement. 2014; 10(6):861-8. DOI: 10.1016/j.jalz.2014.06.015. View

Camporez D, Belcavello L, Ferreira Figueiredo Almeida J, Silva-Sena G, Pimassoni L, Morelato R . Positive association of a Sirt1 variant and parameters of oxidative stress on Alzheimer's disease. Neurol Sci. 2020; 42(5):1843-1851. DOI: 10.1007/s10072-020-04704-y. View

Conejero-Goldberg C, Hyde T, Chen S, Dreses-Werringloer U, Herman M, Kleinman J . Molecular signatures in post-mortem brain tissue of younger individuals at high risk for Alzheimer's disease as based on APOE genotype. Mol Psychiatry. 2010; 16(8):836-47. PMC: 2953572. DOI: 10.1038/mp.2010.57. View

de Chaves E, Narayanaswami V . Apolipoprotein E and cholesterol in aging and disease in the brain. Future Lipidol. 2009; 3(5):505-530. PMC: 2600507. DOI: 10.2217/17460875.3.5.505. View

Bellucci C, Lilli C, Baroni T, Parnetti L, Sorbi S, Emiliani C . Differences in extracellular matrix production and basic fibroblast growth factor response in skin fibroblasts from sporadic and familial Alzheimer's disease. Mol Med. 2007; 13(9-10):542-50. PMC: 1933258. DOI: 10.2119/2007-00034.Bellucci. View

10.

Liu N, Sun J, Wang X, Zhao M, Huang Q, Li H . The Impact of Dementia on the Clinical Outcome of COVID-19: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2020; 78(4):1775-1782. DOI: 10.3233/JAD-201016. View

11.

Rasmussen K, Tybjaerg-Hansen A, Nordestgaard B, Frikke-Schmidt R . APOE and dementia - resequencing and genotyping in 105,597 individuals. Alzheimers Dement. 2020; 16(12):1624-1637. PMC: 7984319. DOI: 10.1002/alz.12165. View

12.

Wang C, Zhang M, Garcia Jr G, Tian E, Cui Q, Chen X . ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response. Cell Stem Cell. 2021; 28(2):331-342.e5. PMC: 7832490. DOI: 10.1016/j.stem.2020.12.018. View

13.

Akter R, Afrose A, Rahman M, Chowdhury R, Nirzhor S, Khan R . A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes. Int J Mol Sci. 2021; 22(8). PMC: 8073883. DOI: 10.3390/ijms22084180. View

14.

Murgolo N, Therien A, Howell B, Klein D, Koeplinger K, Lieberman L . SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development. PLoS Pathog. 2021; 17(2):e1009225. PMC: 7888651. DOI: 10.1371/journal.ppat.1009225. View

15.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

16.

Baggen J, Persoons L, Vanstreels E, Jansen S, Van Looveren D, Boeckx B . Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2. Nat Genet. 2021; 53(4):435-444. DOI: 10.1038/s41588-021-00805-2. View

17.

Wu Y, Zhao Y, Xu T, You L, Zhang H, Liu F . Alzheimer's Disease Affects Severity of Asthma Through Methylation Control of Foxp3 Promoter. J Alzheimers Dis. 2019; 70(1):121-129. DOI: 10.3233/JAD-190315. View

18.

Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P . Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. 2020; 383(16):1522-1534. PMC: 7315890. DOI: 10.1056/NEJMoa2020283. View

19.

Cantuti-Castelvetri L, Ojha R, Pedro L, Djannatian M, Franz J, Kuivanen S . Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020; 370(6518):856-860. PMC: 7857391. DOI: 10.1126/science.abd2985. View

20.

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View