Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype

Bonomi, Chiara Giuseppina; Martorana, Alessandro; Fiorelli, Denise; Nuccetelli, Marzia; Placidi, Fabio; Mercuri, Nicola Biagio; Motta, Caterina

doi:10.3390/ijms25073725

Open AccessArticle

Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype

by

Chiara Giuseppina Bonomi

¹

,

Alessandro Martorana

^1,*

,

Denise Fiorelli

²

,

Marzia Nuccetelli

²,

Fabio Placidi

³,

Nicola Biagio Mercuri

³

and

Caterina Motta

¹

UOSD Memory Clinic, Policlinico Tor Vergata, University of Rome “Tor Vergata”, 00133 Rome, Italy

²

Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy

³

Neurology Unit, Policlinico Tor Vergata, University of Rome “Tor Vergata”, 00133 Rome, Italy

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(7), 3725; https://doi.org/10.3390/ijms25073725

Submission received: 23 February 2024 / Revised: 19 March 2024 / Accepted: 25 March 2024 / Published: 27 March 2024

(This article belongs to the Special Issue Basic, Translational and Clinical Research on Dementia)

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Abstract

Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer’s disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics by comparing the cerebrospinal fluid (CSF) levels of nNOS and eNOS of 8 healthy controls (HC) and 27 patients with a clinical diagnosis of Alzheimer’s disease and isolated CSF amyloid changes, stratified according to APOE ε genotype (APOE ε3 = 13, APOE ε4 = 14). Moreover, we explored the associations between NOS isoforms, CSF AD biomarkers, age, sex, cognitive decline, and blood–brain barrier permeability. In our cohort, both eNOS and nNOS levels were increased in APOE ε3 with respect to HC and APOE ε4. CSF eNOS inversely correlated with CSF Amyloid-β42 selectively in carriers of APOE ε3; CSF nNOS was negatively associated with age and CSF p-tau only in the APOE ε4 subgroup. Increased eNOS could represent compensative vasodilation to face progressive Aβ-induced vasoconstriction in APOE ε3, while nNOS could represent the activation of NO-mediated plasticity strategies in the same group. Our results confirm previous findings that the APOE genotype is linked with different vascular responses to AD pathology.

Keywords: Alzheimer’s disease; nitric oxide synthase; apolipoprotein E; amyloid β

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MDPI and ACS Style

Bonomi, C.G.; Martorana, A.; Fiorelli, D.; Nuccetelli, M.; Placidi, F.; Mercuri, N.B.; Motta, C. Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype. Int. J. Mol. Sci. 2024, 25, 3725. https://doi.org/10.3390/ijms25073725

AMA Style

Bonomi CG, Martorana A, Fiorelli D, Nuccetelli M, Placidi F, Mercuri NB, Motta C. Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype. International Journal of Molecular Sciences. 2024; 25(7):3725. https://doi.org/10.3390/ijms25073725

Chicago/Turabian Style

Bonomi, Chiara Giuseppina, Alessandro Martorana, Denise Fiorelli, Marzia Nuccetelli, Fabio Placidi, Nicola Biagio Mercuri, and Caterina Motta. 2024. "Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype" International Journal of Molecular Sciences 25, no. 7: 3725. https://doi.org/10.3390/ijms25073725

APA Style

Bonomi, C. G., Martorana, A., Fiorelli, D., Nuccetelli, M., Placidi, F., Mercuri, N. B., & Motta, C. (2024). Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype. International Journal of Molecular Sciences, 25(7), 3725. https://doi.org/10.3390/ijms25073725

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Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype

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