Dysfunction of norepinephrine and its metabolites in Alzheimer?s dementia-A review with meta-analysis

Data de publicação: 01/01/2023 Data Ahead of Print: 01/11/2022

Autores da FMUP

• Teresa Sarmento Henriques

  Autor

• Maria Augusta Vieira Coelho

  Autor

• Joana Da Cruz Guimarães Ferreira De Almeida

  Autor

Participantes de fora da FMUP

• Moreira, IP

Unidades de investigação

• Biomedicina

• Neurociências Clínicas e Saúde Mental

Abstract

Some studies point locus coeruleus cell loss, the central nervous system main source of norepinephrine, to be one of the earliest neuropathological events of Alzheimer's disease (AD). However, there are conflicting reports regarding the level of norepinephrine and its metabolites (3-Methoxy-4-hydroxyphenylglycol (MHPG), 3,5-dihy-droxyphenylglycine (DHPG) and 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL)) in AD patients. Uncover these alterations may be a key factor for understanding cognitive deficits and AD pathology. We review the literature that compare norepinephrine and its metabolites between AD patients and non-demented controls. A meta-analysis did not reveal significant statistical differences, but there was a trend towards a lower level of norepinephrine of AD, with almost no difference in MHPG in the cerebrospinal fluid. Regarding MHPG in plasma, DHPG and DOPEGAL we only performed a qualitative analyse due to the small or absent number of studies. These findings point to a decrease in norepinephrine, what is in line with locus coeluleus cell loss in AD. The absence of statistical difference and an equal level of MHGP could indicate a compensatory mechanism.

Keywords

• Dementia; Alzheimer disease; Catecholamine; Norepinephrine; 3-Methoxy-4-hydroxyphenylglycol (MHPG); 35-dihydroxyphenylglycine (DHPG); 34-dihydroxyphenylglycolaldehyde; (DOPEGAL); Meta-analysis