Relationship between cerebrospinal fluid catecholamines levels and biomarkers of Alzheimer’s disease, inflammation and neuronal injury

Changes in the locus coeruleus are among the earliest events in Alzheimer's disease (AD). We aimed to evaluate the relationship between cerebrospinal fluid (CSF) L-dihydroxyphenylalanine (L-DOPA), dopamine, and norepinephrine with CSF biomarkers of AD pathology (β-amyloid and p-tau), neuronal destruction (neurofilaments), and inflammation (leukocytes, IgG index, interleukin-6 and 10). We conducted a cross-sectional, observational study, including 35 patients with AD, 16 with frontotemporal dementia, and 38 normal controls (NC). L-DOPA was lower (p = 0.032) and neurofilaments were higher (p = 0.005) in AD than in NC. Norepinephrine levels were positively correlated with age (r = 0.260, p = 0.015 among all patients). L-DOPA levels were negatively correlated with neurofilaments (r = -0.228, p = 0.038 among all participants). Interleukin-6 was positively correlated with L-DOPA (r = 0.382, p = 0.026) and norepinephrine (r = 0.485, p = 0.004) levels in AD. Since neurofilaments are associated with neuronal damage, decreased L-DOPA levels in AD could be related to neuronal destruction. Catecholaminergic dysregulation seen in AD seems independent of β-amyloid and p-tau pathology.