Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know?
Abstract
:1. Introduction
2. COVID-19 and Dementia: A Bidirectional Risk
3. Different Clinical Presentation of COVID-19 among Dementia Patients
4. Angiotensin-Converting Enzyme 2 (ACE2) Receptor
Overlaps between ACE2 and COVID-19
5. Apolipoprotein E (ApoE)
Overlaps between ApoE and COVID-19
6. Neuroinflammation in AD
6.1. Cytokine Storm and NLRP3 Inflammasome
6.2. Apolipoprotein E
6.3. Acetylcholine
6.4. The Oxidative Stress Hypothesis of AD
7. Mental Health of AD Patients during COVID-19 Pandemic and Associated Social Distancing Measures
7.1. Neuropsychiatric Symptoms and Cognitive Decline
7.2. Nursing Burden and Mental Health of AD Caregivers
8. Conclusions
Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACE | angiotensin-converting enzyme |
ACE2 | angiotensin-converting enzyme 2 |
ACEI | angiotensin-converting enzyme inhibitors |
AChE | acetylcholinesterase |
AD | Alzheimer’s disease |
ALS | amyotrophic lateral sclerosis |
Ang II | angiotensin II |
Ang-(1-7) | angiotensin-(1-7) |
ApoE | apolipoprotein E |
ARBs | Angiotensin II type 1 (AT1) receptor blockers |
BBB | blood-brain barrier |
BDNF | brain-derived neurotrophic factor |
ChAT | choline acetyltransferase |
CI | confidence interval |
CNS | central nervous system |
COPD | chronic obstructive pulmonary disease |
COVID-19 | coronavirus disease 2019 |
CSF | cerebrospinal fluid |
GM-CSF | granulocyte macrophage-colony stimulating factor |
HCV | hepatitis C virus |
HiPSCs | human-induced pluripotent stem cells |
IFN | interferon |
IL-1β | interleukin-1β |
IL-2 | interleukin-2 |
IL-6 | interleukin-6 |
IL-10 | interleukin-10 |
IP-10 | interferon-γ-inducible protein 10 |
HIV | human immunodeficiency virus |
HSV | herpes simplex virus |
mACE2 | membrane-bound ACE2 |
MCP-1 | monocyte chemoattractant protein-1 |
MMSE | Mini-Mental State Examination |
NPI | Neuropsychiatric Inventory |
PD | Parkinson’s disease |
PET | positron emission tomography |
NLRP3 | NLR family pyrin domain-containing protein 3 |
OR | odds ratio |
ORF3a | open reading frame 3a |
RCD | rapid cognitive decline |
ROS | reactive oxygen species |
sACE2 | soluble ACE2 |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
TNF-α | tumor necrosis factor α |
References
- Dumurgier, J.; Sabia, S. Nouvelles tendances épidémiologiques de la maladie d’Alzheimer [Epidemiology of Alzheimer’s disease: Latest trends]. Rev Prat. 2020, 70, 149–151. (In French) [Google Scholar]
- Garre-Olmo, J. Epidemiologia de la enfermedad de Alzheimer y otras demencias [Epidemiology of Alzheimer’s disease and other dementias]. Rev Neurol. 2018, 66, 377–386. (In Spanish) [Google Scholar] [PubMed]
- Mendiola-Precoma, J.; Berumen, L.C.; Padilla, K.; Garcia-Alcocer, G. Therapies for Prevention and Treatment of Alzheimer’s Disease. Biomed Res Int. 2016, 2016, 2589276. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weller, J.; Budson, A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research 2018, 7, 1161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goodman, R.A.; Lochner, K.A.; Thambisetty, M.; Wingo, T.S.; Posner, S.F.; Ling, S.M. Prevalence of dementia subtypes in United States Medicare fee-for-service beneficiaries, 2011–2013. Alzheimers Dement. 2017, 13, 28–37. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Du, X.; Wang, X.; Geng, M. Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener. 2018, 7, 2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piekut, T.; Hurła, M.; Banaszek, N.; Szejn, P.; Dorszewska, J.; Kozubski, W.; Prendecki, M. Infectious agents and Alzheimer’s disease. J. Integr. Neurosci. 2022, 21, 73. [Google Scholar] [CrossRef]
- Seaks, C.E.; Wilcock, D.M. Infectious hypothesis of Alzheimer disease. PLoS Pathog. 2020, 16, e1008596. [Google Scholar] [CrossRef]
- Li, F.; Hearn, M.; Bennett, L.E. The role of microbial infection in the pathogenesis of Alzheimer’s disease and the opportunity for protection by anti-microbial peptides. Crit. Rev. Microbiol. 2021, 47, 240–253. [Google Scholar] [CrossRef]
- Xia, X.; Wang, Y.; Zheng, J. COVID-19 and Alzheimer’s disease: How one crisis worsens the other. Transl. Neurodegener. 2021, 10, 15. [Google Scholar] [CrossRef]
- Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 579, 270–273, Erratum in: Nature 2020, 588, E6. [Google Scholar] [CrossRef] [PubMed]
- Zubair, A.S.; McAlpine, L.S.; Gardin, T.; Farhadian, S.; Kuruvilla, D.E.; Spudich, S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol. 2020, 77, 1018–1027. [Google Scholar] [CrossRef] [PubMed]
- Bostancıklıoğlu, M. Temporal Correlation Between Neurological and Gastrointestinal Symptoms of SARS-CoV-2. Inflamm. Bowel Dis. 2020, 26, e89–e91. [Google Scholar] [CrossRef] [PubMed]
- Misra, S.; Kolappa, K.; Prasad, M.; Radhakrishnan, D.; Thakur, K.T.; Solomon, T.; Michael, B.D.; Winkler, A.S.; Beghi, E.; Guekht, A.; et al. Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis. Neurology. 2021, 97, e2269–e2281. [Google Scholar] [CrossRef]
- Mao, L.; Jin, H.; Wang, M.; Hu, Y.; Chen, S.; He, Q.; Chang, J.; Hong, C.; Zhou, Y.; Wang, D.; et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020, 77, 683–690. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.K.; Cho, Y.J.; Lee, S.Y. Neurological Manifestations in Patients with COVID-19: Experiences from the Central Infectious Diseases Hospital in South Korea. J. Clin. Neurol. 2021, 17, 435–442. [Google Scholar] [CrossRef]
- Taquet, M.; Geddes, J.R.; Husain, M.; Luciano, S.; Harrison, P.J. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. Lancet Psychiatry 2021, 8, 416–427. [Google Scholar] [CrossRef]
- Cilia, R.; Bonvegna, S.; Straccia, G.; Andreasi, N.G.; Elia, A.E.; Romito, L.M.; Devigili, G.; Cereda, E.; Eleopra, R. Effects of COVID-19 on Parkinson’s Disease Clinical Features: A Community-Based Case-Control Study. Mov. Disord. 2020, 35, 1287–1292. [Google Scholar] [CrossRef]
- Brundin, P.; Nath, A.; Beckham, J.D. Is COVID-19 a Perfect Storm for Parkinson’s Disease? Trends Neurosci. 2020, 43, 931–933. [Google Scholar] [CrossRef]
- Lee, S.; Arcila-Londono, X.; Steijlen, K.; Newman, D.; Grover, K. Case report of ALS patient with COVID-19 infection (5032). Neurology 2021, 96 (Suppl. 15), 5032. [Google Scholar]
- Matias-Guiu, J.A.; Delgado-Alonso, C.; Yus, M.; Polidura, C.; Gómez-Ruiz, N.; Valles-Salgado, M.; Ortega-Madueño, I.; Cabrera-Martín, M.N.; Matias-Guiu, J. “Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report. Front. Psychol. 2021, 12, 724022. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Liu, J.; Lin, J.; Shang, H. COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study. Transl. Psychiatry 2022, 12, 283. [Google Scholar] [CrossRef] [PubMed]
- Atkins, J.L.; Masoli, J.A.; Delgado, J.; Pilling, L.C.; Kuo, C.L.; Kuchel, G.A.; Melzer, D. Preexisting Comorbidities Predicting Severe COVID-19 in Older Adults in the UK Biobank Community Cohort. J. Gerontol. Ser. A 2020, 75, 2224–2230. [Google Scholar] [CrossRef]
- Wang, Q.; Davis, P.B.; Gurney, M.E.; Xu, R. COVID-19 and dementia: Analyses of risk, disparity, and outcomes from electronic health records in the US. Alzheimers Dement. 2021, 17, 1297–1306. [Google Scholar] [CrossRef] [PubMed]
- Docherty, A.; Harrison, E.; Green, C.; Hardwick, H.; Pius, R.; Norman, L.; Holden, K.A.; Read, J.M.; Dondelinger, F.; Carson, G.; et al. Features of 16,749 Hospitalised UK Patients with COVID-19 Using the ISARIC WHO Clinical Characterisation Protocol [Internet]. Infectious Diseases (Except HIV/AIDS). April 2020. Available online: http://medrxiv.org/lookup/doi/10.1101/2020.04.23.20076042 (accessed on 28 December 2022).
- 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, 1775–1782. [Google Scholar] [CrossRef]
- Martín-Jiménez, P.; Muñoz-García, M.I.; Seoane, D.; Roca-Rodríguez, L.; García-Reyne, A.; Lalueza, A.; Maestro, G.; Folgueira, D.; Blanco-Palmero, V.A.; Herrero-San Martín, A.; et al. Cognitive Impairment Is a Common Comorbidity in Deceased COVID-19 Patients: A Hospital-Based Retrospective Cohort Study. J. Alzheimers Dis. 2020, 78, 1367–1372. [Google Scholar] [CrossRef] [PubMed]
- Park, H.Y.; Song, I.A.; Oh, T.K. Dementia Risk among Coronavirus Disease Survivors: A Nationwide Cohort Study in South Korea. J. Pers. Med. 2021, 11, 1015. [Google Scholar] [CrossRef]
- Harb, A.A.; Chen, R.; Chase, H.S.; Natarajan, K.; Noble, J.M. Clinical Features and Outcomes of Patients with Dementia Compared to an Aging Cohort Hospitalized During the Initial New York City COVID-19 Wave. J. Alzheimers Dis. 2021, 81, 679–690. [Google Scholar] [CrossRef]
- Vrillon, A.; Mhanna, E.; Aveneau, C.; Lebozec, M.; Grosset, L.; Nankam, D.; Albuquerque, F.; Razou Feroldi, R.; Maakaroun, B.; Pissareva, I.; et al. COVID-19 in adults with dementia: Clinical features and risk factors of mortality-a clinical cohort study on 125 patients. Alzheimers Res. Ther. 2021, 13, 77. [Google Scholar] [CrossRef]
- Bianchetti, A.; Rozzini, R.; Guerini, F.; Boffelli, S.; Ranieri, P.; Minelli, G.; Bianchetti, L.; Trabucchi, M. Clinical Presentation of COVID19 in Dementia Patients. J. Nutr. Health Aging 2020, 24, 560–562. [Google Scholar] [CrossRef]
- Vickers, C.; Hales, P.; Kaushik, V.; Dick, L.; Gavin, J.; Tang, J.; Godbout, K.; Parsons, T.; Baronas, E.; Hsieh, F.; et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J. Biol. Chem. 2002, 277, 14838–14843. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, P.; Sriramula, S.; Lazartigues, E. ACE2/ANG-(1-7)/Mas pathway in the brain: The axis of good. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011, 300, R804–R817. [Google Scholar] [CrossRef] [PubMed]
- Jiang, T.; Gao, L.; Lu, J.; Zhang, Y.D. ACE2-Ang-(1-7)-Mas Axis in Brain: A Potential Target for Prevention and Treatment of Ischemic Stroke. Curr. Neuropharmacol. 2013, 11, 209–217. [Google Scholar] [CrossRef] [PubMed]
- Hellner, K.; Walther, T.; Schubert, M.; Albrecht, D. Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas. Mol. Cell Neurosci. 2005, 29, 427–435. [Google Scholar] [CrossRef]
- Lazaroni, T.L.; Raslan, A.C.; Fontes, W.R.; de Oliveira, M.L.; Bader, M.; Alenina, N.; Moraes, M.F.; Dos Santos, R.A.; Pereira, G.S. Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory. Neurobiol. Learn Mem. 2012, 97, 113–123. [Google Scholar] [CrossRef] [Green Version]
- Phillips, M.I.; de Oliveira, E.M. Brain renin angiotensin in disease. J. Mol. Med. 2008, 86, 715–722. [Google Scholar] [CrossRef]
- Wang, X.L.; Iwanami, J.; Min, L.J.; Tsukuda, K.; Nakaoka, H.; Bai, H.Y.; Shan, B.S.; Kan-No, H.; Kukida, M.; Chisaka, T.; et al. Deficiency of angiotensin-converting enzyme 2 causes deterioration of cognitive function. NPJ Aging Mech. Dis. 2016, 2, 16024. [Google Scholar] [CrossRef] [Green Version]
- Li, N.C.; Lee, A.; Whitmer, R.A.; Kivipelto, M.; Lawler, E.; Kazis, L.E.; Wolozin, B. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: Prospective cohort analysis. BMJ 2010, 340, b5465. [Google Scholar] [CrossRef] [Green Version]
- Jiang, T.; Zhang, Y.D.; Zhou, J.S.; Zhu, X.C.; Tian, Y.Y.; Zhao, H.D.; Lu, H.; Gao, Q.; Tan, L.; Yu, J.T. Angiotensin-(1-7) is Reduced and Inversely Correlates with Tau Hyperphosphorylation in Animal Models of Alzheimer’s Disease. Mol. Neurobiol. 2016, 53, 2489–2497. [Google Scholar] [CrossRef]
- Li, M.Y.; Li, L.; Zhang, Y.; Wang, X.S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis. Poverty 2020, 9, 45. [Google Scholar] [CrossRef]
- Wissing, S.I.; Obeid, R.; Rädle-Hurst, T.; Rohrer, T.; Herr, C.; Schöpe, J.; Geisel, J.; Bals, R.; Abdul-Khaliq, H. Concentrations of Soluble Angiotensin Converting Enzyme 2 (sACE2) in Children and Adults with and without COVID-19. J. Clin. Med. 2022, 11, 6799. [Google Scholar] [CrossRef] [PubMed]
- Gheblawi, M.; Wang, K.; Viveiros, A.; Nguyen, Q.; Zhong, J.C.; Turner, A.J.; Raizada, M.K.; Grant, M.B.; Oudit, G.Y. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ. Res. 2020, 126, 1456–1474. [Google Scholar] [CrossRef] [PubMed]
- Leow, M.K.S. Clarifying the controversial risk-benefit profile of soluble ACE2 in COVID-19. Crit. Care 2020, 24, 396. [Google Scholar] [CrossRef] [PubMed]
- Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020, 367, 1444–1448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, S.; Liu, J.; Miura, Y.; Tanabe, C.; Maeda, T.; Terayama, Y.; Turner, A.J.; Zou, K.; Komano, H. Conversion of Aβ43 to Aβ40 by the successive action of angiotensin-converting enzyme 2 and angiotensin-converting enzyme. J. Neurosci. Res. 2014, 92, 1178–1186. [Google Scholar] [CrossRef] [Green Version]
- Ding, Q.; Shults, N.V.; Gychka, S.G.; Harris, B.T.; Suzuki, Y.J. Protein Expression of Angiotensin-Converting Enzyme 2 (ACE2) is Upregulated in Brains with Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 1687. [Google Scholar] [CrossRef]
- Zou, K.; Liu, J.; Watanabe, A.; Hiraga, S.; Liu, S.; Tanabe, C.; Maeda, T.; Terayama, Y.; Takahashi, S.; Michikawa, M.; et al. Aβ43 is the earliest-depositing Aβ species in APP transgenic mouse brain and is converted to Aβ41 by two active domains of ACE. Am. J. Pathol. 2013, 182, 2322–2331. [Google Scholar] [CrossRef]
- Kim, J.; Onstead, L.; Randle, S.; Price, R.; Smithson, L.; Zwizinski, C.; Dickson, D.W.; Golde, T.; McGowan, E. Abeta40 inhibits amyloid deposition in vivo. J. Neurosci. 2007, 27, 627–633. [Google Scholar] [CrossRef] [Green Version]
- Yan, Y.; Wang, C. Abeta40 protects non-toxic Abeta42 monomer from aggregation. J. Mol. Biol. 2007, 369, 909–916. [Google Scholar] [CrossRef]
- Hasegawa, K.; Yamaguchi, I.; Omata, S.; Gejyo, F.; Naiki, H. Interaction between A beta(1-42) and A beta(1-40) in Alzheimer’s beta-amyloid fibril formation in vitro. Biochemistry 1999, 38, 15514–15521. [Google Scholar] [CrossRef]
- Hsu, J.T.; Tien, C.F.; Yu, G.Y.; Shen, S.; Lee, Y.H.; Hsu, P.C.; Wang, Y.; Chao, P.K.; Tsay, H.J.; Shie, F.S. The Effects of Aβ1-42 Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2. Int. J. Mol. Sci. 2021, 22, 8226. [Google Scholar] [CrossRef] [PubMed]
- Rao, Y.L.; Ganaraja, B.; Murlimanju, B.V.; Joy, T.; Krishnamurthy, A.; Agrawal, A. Hippocampus and its involvement in Alzheimer’s disease: A review. 3 Biotech. 2022, 12, 55. [Google Scholar] [CrossRef] [PubMed]
- Evans, C.E.; Miners, J.S.; Piva, G.; Willis, C.L.; Heard, D.M.; Kidd, E.J.; Good, M.A.; Kehoe, P.G. ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease. Acta Neuropathol. 2020, 139, 485–502, Erratum in: Acta Neuropathol. 2020, 140, 791. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kamel, A.S.; Abdelkader, N.F.; Abd El-Rahman, S.S.; Emara, M.; Zaki, H.F.; Khattab, M.M. Stimulation of ACE2/ANG(1-7)/Mas Axis by Diminazene Ameliorates Alzheimer’s Disease in the D-Galactose-Ovariectomized Rat Model: Role of PI3K/Akt Pathway. Mol. Neurobiol. 2018, 55, 8188–8202. [Google Scholar] [CrossRef]
- Duan, R.; Xue, X.; Zhang, Q.Q.; Wang, S.Y.; Gong, P.Y.; Yan, E.; Jiang, T.; Zhang, Y.D. ACE2 activator diminazene aceturate ameliorates Alzheimer’s disease-like neuropathology and rescues cognitive impairment in SAMP8 mice. Aging 2020, 12, 14819–14829. [Google Scholar] [CrossRef]
- Zhao, Y.; Li, W.; Lukiw, W. Ubiquity of the SARS-CoV-2 receptor ACE2 and upregulation in limbic regions of Alzheimer’s disease brain. Folia Neuropathol. 2021, 59, 232–238. [Google Scholar] [CrossRef]
- Motaghinejad, M.; Gholami, M. Possible Neurological and Mental Outcomes of COVID-19 Infection: A Hypothetical Role of ACE-2\Mas\BDNF Signaling Pathway. Int. J. Prev. Med. 2020, 11, 84. [Google Scholar] [CrossRef]
- Motaghinejad, M.; Motevalian, M.; Falak, R.; Heidari, M.; Sharzad, M.; Kalantari, E. Neuroprotective effects of various doses of topiramate against methylphenidate-induced oxidative stress and inflammation in isolated rat amygdala: The possible role of CREB/BDNF signaling pathway. J. Neural Transm. 2016, 123, 1463–1477. [Google Scholar] [CrossRef]
- Hauser, P.S.; Narayanaswami, V.; Ryan, R.O. Apolipoprotein E: From lipid transport to neurobiology. Prog. Lipid Res. 2011, 50, 62–74. [Google Scholar] [CrossRef] [Green Version]
- Kim, J.; Basak, J.M.; Holtzman, D.M. The role of apolipoprotein E in Alzheimer’s disease. Neuron 2009, 63, 287–303. [Google Scholar] [CrossRef] [Green Version]
- Korwek, K.M.; Trotter, J.H.; Ladu, M.J.; Sullivan, P.M.; Weeber, E.J. ApoE isoform-dependent changes in hippocampal synaptic function. Mol. Neurodegener. 2009, 4, 21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Drouet, B.; Fifre, A.; Pinçon-Raymond, M.; Vandekerckhove, J.; Rosseneu, M.; Guéant, J.L.; Chambaz, J.; Pillot, T. ApoE protects cortical neurones against neurotoxicity induced by the non-fibrillar C-terminal domain of the amyloid-beta peptide. J. Neurochem. 2001, 76, 117–127. [Google Scholar] [CrossRef] [PubMed]
- Verghese, P.B.; Castellano, J.M.; Holtzman, D.M. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurol. 2011, 10, 241–252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuo, C.L.; Pilling, L.C.; Atkins, J.L.; Masoli, J.A.H.; Delgado, J.; Kuchel, G.A.; Melzer, D. APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort. J. Gerontol. A Biol. Sci. Med. Sci. 2020, 75, 2231–2232. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Zhang, M.; Garcia GJr Tian, E.; Cui, Q.; Chen, X.; Sun, G.; Wang, J.; Arumugaswami, V.; Shi, Y. ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response. Cell Stem Cell 2021, 28, 331–342.e5. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Yuan, Z.; Pavel, M.A.; Jablonski, S.M.; Jablonski, J.; Hobson, R.; Valente, S.; Reddy, C.B.; Hansen, S.B. The role of high cholesterol in age-related COVID19 lethality. bioRxiv 2021. Preprint. [Google Scholar] [CrossRef]
- Fuior, E.V.; Gafencu, A.V. Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond. Int. J. Mol. Sci. 2019, 20, 5939. [Google Scholar] [CrossRef] [Green Version]
- Kuhlmann, I.; Minihane, A.M.; Huebbe, P.; Nebel, A.; Rimbach, G. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: A literature review. Lipids Health Dis. 2010, 9, 8. [Google Scholar] [CrossRef] [Green Version]
- Kinney, J.W.; Bemiller, S.M.; Murtishaw, A.S.; Leisgang, A.M.; Salazar, A.M.; Lamb, B.T. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 2018, 4, 575–590. [Google Scholar] [CrossRef]
- Rubio-Perez, J.M.; Morillas-Ruiz, J.M. A review: Inflammatory process in Alzheimer’s disease, role of cytokines. Sci. World J. 2012, 2012, 756357. [Google Scholar] [CrossRef]
- Kim, Y.S.; Lee, K.J.; Kim, H. Serum tumour necrosis factor-α and interleukin-6 levels in Alzheimer’s disease and mild cognitive impairment. Psychogeriatrics 2017, 17, 224–230. [Google Scholar] [CrossRef] [PubMed]
- Singh-Manoux, A.; Dugravot, A.; Brunner, E.; Kumari, M.; Shipley, M.; Elbaz, A.; Kivimaki, M. Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife. Neurology 2014, 83, 486–493. [Google Scholar] [CrossRef] [PubMed]
- Zanza, C.; Romenskaya, T.; Manetti, A.C.; Franceschi, F.; La Russa, R.; Bertozzi, G.; Maiese, A.; Savioli, G.; Volonnino, G.; Longhitano, Y. Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina 2022, 58, 144. [Google Scholar] [CrossRef] [PubMed]
- Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506, Erratum in: Lancet 2020, 395, 496. [Google Scholar] [CrossRef] [Green Version]
- Chen, L.; Liu, H.G.; Liu, W.; Liu, J.; Liu, K.; Shang, J.; Deng, Y.; Wei, S. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He Hu Xi Za Zhi 2020, 43, E005. (In Chinese) [Google Scholar] [CrossRef]
- Zhu, Z.; Cai, T.; Fan, L.; Lou, K.; Hua, X.; Huang, Z.; Gao, G. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int. J. Infect. Dis. 2020, 95, 332–339. [Google Scholar] [CrossRef]
- Del Valle, D.M.; Kim-Schulze, S.; Huang, H.H.; Beckmann, N.D.; Nirenberg, S.; Wang, B.; Lavin, Y.; Swartz, T.H.; Madduri, D.; Stock, A.; et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat. Med. 2020, 26, 1636–1643. [Google Scholar] [CrossRef] [PubMed]
- Ruan, Q.; Yang, K.; Wang, W.; Jiang, L.; Song, J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020, 46, 846–848, Erratum in: Intensive Care Med. 2020, 46, 1294–1297. [Google Scholar] [CrossRef] [Green Version]
- Reghunathan, R.; Jayapal, M.; Hsu, L.Y.; Chng, H.H.; Tai, D.; Leung, B.P.; Melendez, A.J. Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome. BMC Immunol. 2005, 6, 2. [Google Scholar] [CrossRef] [Green Version]
- Law, H.K.; Cheung, C.Y.; Ng, H.Y.; Sia, S.F.; Chan, Y.O.; Luk, W.; Nicholls, J.M.; Peiris, J.S.; Lau, Y.L. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood 2005, 106, 2366–2374. [Google Scholar] [CrossRef] [Green Version]
- Ren, Y.; Shu, T.; Wu, D.; Mu, J.; Wang, C.; Huang, M.; Han, Y.; Zhang, X.Y.; Zhou, W.; Qiu, Y.; et al. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cell Mol. Immunol. 2020, 17, 881–883. [Google Scholar] [CrossRef] [PubMed]
- Bianchi, M.; Borsetti, A.; Ciccozzi, M.; Pascarella, S. SARS-Cov-2 ORF3a: Mutability and function. Int. J. Biol. Macromol. 2021, 170, 820–826. [Google Scholar] [CrossRef] [PubMed]
- Stancu, I.C.; Cremers, N.; Vanrusselt, H.; Couturier, J.; Vanoosthuyse, A.; Kessels, S.; Lodder, C.; Brône, B.; Huaux, F.; Octave, J.N.; et al. Aggregated Tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo. Acta Neuropathol. 2019, 137, 599–617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heneka, M.T.; Kummer, M.P.; Stutz, A.; Delekate, A.; Schwartz, S.; Vieira-Saecker, A.; Griep, A.; Axt, D.; Remus, A.; Tzeng, T.C.; et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 2013, 493, 674–678. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tejera, D.; Mercan, D.; Sanchez-Caro, J.M.; Hanan, M.; Greenberg, D.; Soreq, H.; Latz, E.; Golenbock, D.; Heneka, M.T. Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome. EMBO J. 2019, 38, e101064. [Google Scholar] [CrossRef] [PubMed]
- Liang, T.; Zhang, Y.; Wu, S.; Chen, Q.; Wang, L. The Role of NLRP3 Inflammasome in Alzheimer’s Disease and Potential Therapeutic Targets. Front. Pharmacol. 2022, 13, 845185. [Google Scholar] [CrossRef]
- Gale, S.C.; Gao, L.; Mikacenic, C.; Coyle, S.M.; Rafaels, N.; Murray Dudenkov, T.; Madenspacher, J.H.; Draper, D.W.; Ge, W.; Aloor, J.J.; et al. APOε4 is associated with enhanced in vivo innate immune responses in human subjects. J. Allergy Clin. Immunol. 2014, 134, 127–134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sam, C.; Bordoni, B. Physiology, Acetylcholine. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. Available online: http://www.ncbi.nlm.nih.gov/books/NBK557825/ (accessed on 15 December 2022).
- Micheau, J.; Marighetto, A. Acetylcholine and memory: A long, complex and chaotic but still living relationship. Behav. Brain Res. 2011, 221, 424–429. [Google Scholar] [CrossRef] [PubMed]
- Borovikova, L.V.; Ivanova, S.; Zhang, M.; Yang, H.; Botchkina, G.I.; Watkins, L.R.; Wang, H.; Abumrad, N.; Eaton, J.W.; Tracey, K.J. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000, 405, 458–462. [Google Scholar] [CrossRef] [PubMed]
- Martinez, A.; Castro, A. Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer’s disease. Expert Opin. Investig. Drugs 2006, 15, 1–12. [Google Scholar] [CrossRef]
- Geula, C.; Nagykery, N.; Nicholas, A.; Wu, C.K. Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease. J. Neuropathol. Exp. Neurol. 2008, 67, 309–318. [Google Scholar] [CrossRef] [Green Version]
- Yiannopoulou, K.G.; Papageorgiou, S.G. Current and Future Treatments in Alzheimer Disease: An Update. J. Cent. Nerv. Syst. Dis. 2020, 12, 1179573520907397. [Google Scholar] [CrossRef] [PubMed]
- Fragoso-Saavedra, S.; Núñez, I.; Audelo-Cruz, B.M.; Arias-Martínez, S.; Manzur-Sandoval, D.; Quintero-Villegas, A.; Benjamín García-González, H.; Carbajal-Morelos, S.L.; PoncedeLeón-Rosales, S.; Gotés-Palazuelos, J.; et al. Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial. Mol. Med. 2022, 28, 131. [Google Scholar] [CrossRef] [PubMed]
- Chowdhury, P.; Pathak, P. Neuroprotective immunity by essential nutrient “Choline” for the prevention of SARS CoV2 infections: An in silico study by molecular dynamics approach. Chem. Phys. Lett. 2020, 761, 138057. [Google Scholar] [CrossRef]
- Zhao, Y.; Zhao, B. Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid. Med. Cell. Longev. 2013, 2013, 316523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, F.; Calingasan, N.Y.; Yu, F.; Mauck, W.M.; Toidze, M.; Almeida, C.G.; Takahashi, R.H.; Carlson, G.A.; Flint Beal, M.; Lin, M.T.; et al. Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J. Neurochem. 2004, 89, 1308–1312. [Google Scholar] [CrossRef] [PubMed]
- Nishida, Y.; Yokota, T.; Takahashi, T.; Uchihara, T.; Jishage, K.; Mizusawa, H. Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse. Biochem. Biophys. Res. Commun. 2006, 350, 530–536. [Google Scholar] [CrossRef]
- Matsuoka, Y.; Picciano, M.; La Francois, J.; Duff, K. Fibrillar beta-amyloid evokes oxidative damage in a transgenic mouse model of Alzheimer’s disease. Neuroscience 2001, 104, 609–613. [Google Scholar] [CrossRef]
- Smith, M.A.; Hirai, K.; Hsiao, K.; Pappolla, M.A.; Harris, P.L.; Siedlak, S.L.; Tabaton, M.; Perry, G. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J. Neurochem. 1998, 70, 2212–2215. [Google Scholar] [CrossRef]
- Mohmmad Abdul, H.; Sultana, R.; Keller, J.N.; St Clair, D.K.; Markesbery, W.R.; Butterfield, D.A. Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: Implications for Alzheimer’s disease. J. Neurochem. 2006, 96, 1322–1335. [Google Scholar] [CrossRef]
- Manczak, M.; Anekonda, T.S.; Henson, E.; Park, B.S.; Quinn, J.; Reddy, P.H. Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum. Mol. Genet. 2006, 15, 1437–1449. [Google Scholar] [CrossRef]
- Apelt, J.; Bigl, M.; Wunderlich, P.; Schliebs, R. Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology. Int. J. Dev. Neurosci. 2004, 22, 475–484. [Google Scholar] [CrossRef] [PubMed]
- Gamblin, T.C.; King, M.E.; Kuret, J.; Berry, R.W.; Binder, L.I. Oxidative regulation of fatty acid-induced tau polymerization. Biochemistry 2000, 39, 14203–14210. [Google Scholar] [CrossRef] [PubMed]
- Melov, S.; Adlard, P.A.; Morten, K.; Johnson, F.; Golden, T.R.; Hinerfeld, D.; Schilling, B.; Mavros, C.; Masters, C.L.; Volitakis, I.; et al. Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS ONE 2007, 2, e536. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murakami, K.; Murata, N.; Noda, Y.; Tahara, S.; Kaneko, T.; Kinoshita, N.; Hatsuta, H.; Murayama, S.; Barnham, K.J.; Irie, K.; et al. SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid β protein oligomerization and memory loss in mouse model of Alzheimer disease. J. Biol. Chem. 2011, 286, 44557–44568. [Google Scholar] [CrossRef] [Green Version]
- Goedert, M.; Hasegawa, M.; Jakes, R.; Lawler, S.; Cuenda, A.; Cohen, P. Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases. FEBS Lett. 1997, 409, 57–62. [Google Scholar] [CrossRef]
- Zhu, X.; Rottkamp, C.A.; Boux, H.; Takeda, A.; Perry, G.; Smith, M.A. Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease. J. Neuropathol. Exp. Neurol. 2000, 59, 880–888. [Google Scholar] [CrossRef] [Green Version]
- Fraga, C.G.; Shigenaga, M.K.; Park, J.W.; Degan, P.; Ames, B.N. Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc. Natl. Acad. Sci. USA 1990, 87, 4533–4537. [Google Scholar] [CrossRef] [Green Version]
- Hamilton, M.L.; Van Remmen, H.; Drake, J.A.; Yang, H.; Guo, Z.M.; Kewitt, K.; Walter, C.A.; Richardson, A. Does oxidative damage to DNA increase with age? Proc. Natl. Acad. Sci. USA 2001, 98, 10469–10474. [Google Scholar] [CrossRef] [Green Version]
- Oliver, C.N.; Ahn, B.W.; Moerman, E.J.; Goldstein, S.; Stadtman, E.R. Age-related changes in oxidized proteins. J. Biol. Chem. 1987, 262, 5488–5491. [Google Scholar] [CrossRef]
- Kozlov, E.M.; Ivanova, E.; Grechko, A.V.; Wu, W.K.; Starodubova, A.V.; Orekhov, A.N. Involvement of Oxidative Stress and the Innate Immune System in SARS-CoV-2 Infection. Diseases 2021, 9, 17. [Google Scholar] [CrossRef]
- Cecchini, R.; Cecchini, A.L. SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med. Hypotheses 2020, 143, 110102. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Qin, R.; Zhang, J.; Chen, Y. Possible immunity, inflammation, and oxidative stress mechanisms of Alzheimer’s disease in COVID-19 patients. Clin. Neurol. Neurosurg. 2021, 201, 106414. [Google Scholar] [CrossRef] [PubMed]
- Muñoz, P.; Ardiles, Á.O.; Pérez-Espinosa, B.; Núñez-Espinosa, C.; Paula-Lima, A.; González-Billault, C.; Espinosa-Parrilla, Y. Redox modifications in synaptic components as biomarkers of cognitive status, in brain aging and disease. Mech. Ageing Dev. 2020, 189, 111250. [Google Scholar] [CrossRef]
- Bonati, M.; Campi, R.; Segre, G. Psychological impact of the quarantine during the COVID-19 pandemic on the general European adult population: A systematic review of the evidence. Epidemiol. Psychiatr. Sci. 2022, 31, e27. [Google Scholar] [CrossRef] [PubMed]
- El Haj, M.; Altintas, E.; Chapelet, G.; Kapogiannis, D.; Gallouj, K. High depression and anxiety in people with Alzheimer’s disease living in retirement homes during the covid-19 crisis. Psychiatry Res. 2020, 291, 113294. [Google Scholar] [CrossRef] [PubMed]
- El Haj, M.; Moustafa, A.A.; Gallouj, K. Higher Depression of Patients with Alzheimer’s Disease During than Before the Lockdown. J. Alzheimers Dis. 2021, 81, 1375–1379. [Google Scholar] [CrossRef] [PubMed]
- Soldevila-Domenech, N.; Forcano, L.; Boronat, A.; Lorenzo, T.; Piera, I.; Puig-Pijoan, A.; Mateus, J.; González de Echevarri Gómez, J.M.; Knezevic, I.; Soteras, A.; et al. Effects of COVID-19 Home Confinement on Mental Health in Individuals with Increased Risk of Alzheimer’s Disease. J. Alzheimers Dis. 2021, 79, 1015–1021. [Google Scholar] [CrossRef]
- Akinci, M.; Peña-Gómez, C.; Operto, G.; Fuentes-Julian, S.; Deulofeu, C.; Sánchez-Benavides, G.; Milà-Alomà, M.; Grau-Rivera, O.; Gramunt, N.; ALFA Study; et al. Prepandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults. Neurology 2022, 99, e1486–e1498. [Google Scholar] [CrossRef]
- El Haj, M.; Larøi, F.; Gallouj, K. Hallucinations and Covid-19: Increased Occurrence of Hallucinations in Patients with Alzheimer’s Disease During Lockdown. Psychiatr. Q. 2021, 92, 1531–1539. [Google Scholar] [CrossRef]
- Gan, J.; Liu, S.; Wu, H.; Chen, Z.; Fei, M.; Xu, J.; Dou, Y.; Wang, X.; Ji, Y. The Impact of the COVID-19 Pandemic on Alzheimer’s Disease and Other Dementias. Front. Psychiatry 2021, 12, 703481. [Google Scholar] [CrossRef] [PubMed]
- Boutoleau-Bretonnière, C.; Pouclet-Courtemanche, H.; Gillet, A.; Bernard, A.; Deruet, A.L.; Gouraud, I.; Mazoue, A.; Lamy, E.; Rocher, L.; Kapogiannis, D.; et al. The Effects of Confinement on Neuropsychiatric Symptoms in Alzheimer’s Disease During the COVID-19 Crisis. J. Alzheimers Dis. 2020, 76, 41–47. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.C.; Liu, S.; Gan, J.; Ma, L.; Du, X.; Zhu, H.; Han, J.; Xu, J.; Wu, H.; Fei, M.; et al. The Impact of the COVID-19 Pandemic and Lockdown on Mild Cognitive Impairment, Alzheimer’s Disease and Dementia With Lewy Bodies in China: A 1-Year Follow-Up Study. Front. Psychiatry 2021, 12, 711658. [Google Scholar] [CrossRef]
- Bao, X.; Xu, J.; Meng, Q.; Gan, J.; Wang, X.D.; Wu, H.; Liu, S.; Ji, Y. Impact of the COVID-19 Pandemic and Lockdown on Anxiety, Depression and Nursing Burden of Caregivers in Alzheimer’s Disease, Dementia With Lewy Bodies and Mild Cognitive Impairment in China: A 1-Year Follow-Up Study. Front. Psychiatry 2022, 13, 921535. [Google Scholar] [CrossRef] [PubMed]
- Bakker, E.D.; van Maurik, I.S.; Mank, A.; Zwan, M.D.; Waterink, L.; van den Buuse, S.; van den Broeke, J.R.; Gillissen, F.; van de Beek, M.; Lemstra, E.; et al. Psychosocial Effects of COVID-19 Measures on (Pre-)Dementia Patients During Second Lockdown. J. Alzheimers Dis. 2022, 86, 931–939. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Rudnicka-Drożak, E.; Drożak, P.; Mizerski, G.; Zaborowski, T.; Ślusarska, B.; Nowicki, G.; Drożak, M. Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know? Int. J. Environ. Res. Public Health 2023, 20, 2146. https://doi.org/10.3390/ijerph20032146
Rudnicka-Drożak E, Drożak P, Mizerski G, Zaborowski T, Ślusarska B, Nowicki G, Drożak M. Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know? International Journal of Environmental Research and Public Health. 2023; 20(3):2146. https://doi.org/10.3390/ijerph20032146
Chicago/Turabian StyleRudnicka-Drożak, Ewa, Paulina Drożak, Grzegorz Mizerski, Tomasz Zaborowski, Barbara Ślusarska, Grzegorz Nowicki, and Martyna Drożak. 2023. "Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know?" International Journal of Environmental Research and Public Health 20, no. 3: 2146. https://doi.org/10.3390/ijerph20032146