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.