3 research outputs found
5-HT7 receptors in Alzheimer's disease
Even though the involvement of serotonin (5-hydroxytryptamine; 5-HT) and its receptors in Alzheimer’s disease
(AD) is widely accepted, data on the expression and the role of 5-HT7 receptors in AD is relatively limited.
Therefore, the objective of the present work was to study the expression of serotonergic 5-HT7 receptors in
postmortem samples of AD brains and correlate it with neurotransmitter levels, cognition and behavior. The
study population consisted of clinically well-characterized and neuropathologically confirmed AD patients (n =
42) and age-matched control subjects (n = 18). Reverse-transcription quantitative polymerase chain reaction
(RT-qPCR) and high-performance liquid chromatography were performed on Brodmann area (BA) 7, BA10,
BA22, BA24, hippocampus, amygdala, thalamus and cerebellum to measure mRNA levels of 5-HT7 receptors
(HTR7), as well as the concentrations of various monoamine neurotransmitters and their metabolites.
Decreased levels of HTR7 mRNA were observed in BA10. A significant association was observed between
HTR7 levels in BA10 and BEHAVE-AD cluster B (hallucinations) (rs(28) = 0.444, P < 0.05). In addition, a
negative correlation was observed between HTR7 levels in BA10 and both MHPG concentrations in this brain
region (rs(45) = -0.311; P < 0.05), and DOPAC levels in the amygdala (rs(42) = -0.311; P < 0.05). Quite sur-
prisingly, no association was found between HTR7 levels and cognitive status. Altogether, this study supports the notion of the involvement of 5-HT7 receptors in psychotic symptoms in AD, suggesting the interest of testing antagonist acting at this receptor to specifically treat psychotic symptoms in this illness
5-HT7 receptors in Alzheimer's disease
Even though the involvement of serotonin (5-hydroxytryptamine; 5-HT) and its receptors in Alzheimer’s disease
(AD) is widely accepted, data on the expression and the role of 5-HT7 receptors in AD is relatively limited.
Therefore, the objective of the present work was to study the expression of serotonergic 5-HT7 receptors in
postmortem samples of AD brains and correlate it with neurotransmitter levels, cognition and behavior. The
study population consisted of clinically well-characterized and neuropathologically confirmed AD patients (n =
42) and age-matched control subjects (n = 18). Reverse-transcription quantitative polymerase chain reaction
(RT-qPCR) and high-performance liquid chromatography were performed on Brodmann area (BA) 7, BA10,
BA22, BA24, hippocampus, amygdala, thalamus and cerebellum to measure mRNA levels of 5-HT7 receptors
(HTR7), as well as the concentrations of various monoamine neurotransmitters and their metabolites.
Decreased levels of HTR7 mRNA were observed in BA10. A significant association was observed between
HTR7 levels in BA10 and BEHAVE-AD cluster B (hallucinations) (rs(28) = 0.444, P < 0.05). In addition, a
negative correlation was observed between HTR7 levels in BA10 and both MHPG concentrations in this brain
region (rs(45) = -0.311; P < 0.05), and DOPAC levels in the amygdala (rs(42) = -0.311; P < 0.05). Quite sur-
prisingly, no association was found between HTR7 levels and cognitive status. Altogether, this study supports the notion of the involvement of 5-HT7 receptors in psychotic symptoms in AD, suggesting the interest of testing antagonist acting at this receptor to specifically treat psychotic symptoms in this illness
Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort
TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal
dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in
the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer’s disease
(EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are
enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against
2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically
diagnosed with Alzheimer’s disease and a positive family history of ALS. We did not observe enrichment
of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFkB induction. Of 3
common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13e1.9]; p-value
0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our
findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between
common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS
cohorts