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Established amyloid-? pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine.

ABSTRACT:

Introduction

Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-? (A?) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action.

Methods

We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates A? pathology in plaque-bearing double-transgenic amyloid precursor protein (APP)_swe/presenilin 1 (PS1)_?E9 mutants. In addition, we addressed whether serotonin depletion affects A? pathology. Treatments were assessed by measurement of serotonin transporter occupancy and high-performance liquid chromatography. The effect of paroxetine on A? pathology was evaluated by stereological plaque load estimation and A?₄₂/A?₄₀ ratio by enzyme-linked immunosorbent assay.

Results

Contrary to our hypothesis, paroxetine therapy did not mitigate A? pathology, and depletion of brain serotonin did not exacerbate A? pathology. However, chronic paroxetine therapy increased mortality in APP_swe/PS1_?E9 transgenic mice.

Discussion

Our results question the ability of selective serotonin reuptake inhibitor therapy to ameliorate established A? pathology. The severe adverse effect of paroxetine may discourage its use for disease-modifying purposes in Alzheimer's disease.

SUBMITTER: Severino M

PROVIDER: S-EPMC6021554 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine.

Severino Maurizio M Sivasaravanaparan Mithula M Olesen Louise Ø LØ von Linstow Christian U CU Metaxas Athanasios A Bouzinova Elena V EV Khan Asif Manzoor AM Lambertsen Kate L KL Babcock Alicia A AA Gramsbergen Jan Bert JB Wiborg Ove O Finsen Bente B

Alzheimer's & dementia (New York, N. Y.) 20180524

<h4>Introduction</h4>Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action.<h4>Methods</h4>We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic amyloid precursor protein (APP)<sub>swe</sub>/presenilin 1 (PS1)<sub>ΔE9</sub> mutants. In addition, we addressed w ...[more]

PMID: 29955664

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