Serotonin-2B receptor (5-HTR) expression and binding in the brain of APP/PS1 transgenic mice and in Alzheimer's disease brain tissue.

Despite well-documented dysregulation in central serotonergic signaling in Alzheimer's disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HTR) subtype remains sparse. Here, we assessed the levels of 5-HTRs in brain tissue from APP/PS1 transgenic (TG) mice, AD patients, and adult microglial cells. 5-HTR mRNA was measured by RT-qPCR in ageing TG and wild-type (WT) mice, in samples from the middle frontal gyrus of female, AD and control subjects, and in microglia from the cerebral cortex of WT mice.

The Combined Effects of Amyloidosis and Serotonin Deficiency by Tryptophan Hydroxylase-2 Knockout Impacts Viability of the APP/PS1 Mouse Model of Alzheimer's Disease.

Background: A decline of brain serotonin (5-HT) is held responsible for the changes in mood that can be observed in Alzheimer's disease (AD). However, 5-HT'ergic signaling is also suggested to reduce the production of pathogenic amyloid-β (Aβ).

Objective: To investigate the effect of targeted inactivation of tryptophan hydroxylase-2 (Tph2), which is essential for neuronal 5-HT synthesis, on amyloidosis in amyloid precursor protein (APP)swe/presenilin 1 (PS1) ΔE9 transgenic mice.

Ageing and amyloidosis underlie the molecular and pathological alterations of tau in a mouse model of familial Alzheimer's disease.

Despite compelling evidence that the accumulation of amyloid-beta (Aβ) promotes neocortical MAPT (tau) aggregation in familial and idiopathic Alzheimer's disease (AD), murine models of cerebral amyloidosis are not considered to develop tau-associated pathology. In the present study, we show that tau can accumulate spontaneously in aged transgenic APP/PS1 mice. Tau pathology is abundant around Aβ deposits, and further characterized by accumulation of Gallyas and thioflavin-S-positive inclusions, which were detected in the APP/PS1 brain at 18 months of age.

Neuroinflammation and amyloid-beta 40 are associated with reduced serotonin transporter (SERT) activity in a transgenic model of familial Alzheimer's disease.

Background: Discrepant and often contradictory results have accumulated regarding the antidepressant and pro-cognitive effects of serotonin transporter (SERT) antagonists in Alzheimer's disease.

Methods: To address the discrepancy, we measured the activity and density of SERT in the neocortex of 3-24-month-old APP/PS1 and wild-type littermate mice, by using [H]DASB autoradiography and the [H]5-HT uptake assay. Levels of soluble amyloid-β (Aβ), and pro-inflammatory cytokines that can regulate SERT function, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF), were measured in parallel.