Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation

Autor: Roberto Aquilani, Matteo Cotta Ramusino, Roberto Maestri, Paolo Iadarola, Mirella Boselli, Giulia Perini, Federica Boschi, Maurizia Dossena, Anna Bellini, Daniela Buonocore, Enrico Doria, Alfredo Costa, Manuela Verri
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Aging Neuroscience, Vol 15 (2023)
Druh dokumentu: article
ISSN: 1663-4365
DOI: 10.3389/fnagi.2023.1237469
Popis: ObjectiveDementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission.Materials and methodsSixty-five demented patients (Alzheimer’s disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants.ResultsDemented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to
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