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French maritime pine bark treatment decelerates plaque development and improves spatial memory in Alzheimer's disease mice


Year of Publication:
Contact PI Name:
Jens Pahnke
Contact PI Affiliation:
Department of Neuro/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Oslo, Norway
K. Paarmann, S.R. Prakash, M. Krohn, L. Mohle, M. Brackhan, T. Bruning, I. Eiriz
Primary Reference (PubMED ID):
Funding Source:
Deutsche Forschungsgemeinschaft/German Research Foundation
EU Joint Programme-Neurodegenerative Disease Research (JPND)
Leibniz Association Germany
Norsk Forskningsradet
State Education Development Agency Republic of Latvia (VIAA)
Study Goal and Principal Findings:

Background: Plant extracts are increasingly investigated as potential drugs against Alzheimer's disease (AD) and dementia in general. Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects.

Hypothesis/Purpose: Pycnogenol is thought to improve cognitive functions in elderly. We wanted to investigate and quantify these effects in a model system of cerebral β-amyloidosis/AD.

Study design/methods: This study experimentally assessed the effects of Pycnogenol on AD-related pathology in a β-amyloidosis mouse model. APP-transgenic mice and controls were treated orally in a pre-onset and post-onset treatment paradigm. The effects of Pycnogenol were characterized by analysing β-amyloid (Aβ) plaques, number of neurons, glia coverage, myelination pattern, and cortical coverage with axons using immunohistochemistry. As levels were quantified using ELISA and gene expression levels of APP-processing enzymes ADAM10, BACE1 and IDE protein levels were determined by Western blot. Behavioural changes in circadian rhythm were monitored and spatial memory / cognition was assessed using a water maze test.

Results: Pycnogenol significantly decreased the number of plaques in both treatment paradigms but did not alter levels of soluble Aβ or the gene expression of APP-processing enzymes. The morphological analyses revealed no changes in the number of neurons, astrocytes, microglia, the myelination pattern, or the morphology of axons. Behavioural testing revealed an improvement of the spatial memory in the pre-onset treatment paradigm only.

Conclusion: Our results suggest to evaluate clinically a potential use of Pycnogenol in the prevention or in early stages of mild cognitive impairment (MCI) and AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Morris Water Maze
Motor Function
Locomotor Activity
Swimming Speed
beta Amyloid Deposits
beta Amyloid Load
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-Guanidine Soluble beta Amyloid Peptide 42
A Disintegrin and Metalloproteinase Domain 10 (ADAM10)
beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)
Insulin Degrading Enzyme (IDE)
Amyloid Plaque Size
Brain-beta Amyloid Deposits
Glial Fibrillary Acidic Protein (GFAP)
Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
Myelin Basic Protein
Neuronal Marker NeuN
Neuronal Nitric Oxide Synthase (nNOS/NOS1)
Cell Count