Abstract

.We implemented a wide field-of-view visible-light optical coherence microscope (OCM) for investigating ex-vivo brain tissue of patients diagnosed with Alzheimer’s disease (AD) and of a mouse model of AD. A submicrometer axial resolution in tissue was achieved using a broad visible light spectrum. The use of various objective lenses enabled reaching micrometer transversal resolution and the acquisition of images of microscopic brain features, such as cell structures, vessels, and white matter tracts. Amyloid-beta plaques in the range of 10 to were visualized. Large field-of-view images of young and old mouse brain sections were imaged using an automated stage. The plaque load was characterized, revealing an age-related increase. Human brain tissue affected by cerebral amyloid angiopathy was investigated and hyperscattering structures resembling amyloid beta accumulations in the vessel walls were identified. All results were in good agreement with histology. A comparison of plaque features in both human and mouse brain tissue was performed, revealing an increase in plaque load and a decrease in reflectivity for mouse as compared with human brain tissue. Based on the promising outcome of our experiments, visible light OCM might be a powerful tool for investigating microscopic features in ex-vivo brain tissue.

Highlights

  • One out of nine Americans aged above 65 years is suffering from Alzheimer’s disease (AD), making it the most common form of dementia worldwide.[1]

  • amyloid precursor protein (APP)-presenilin 1 (PS1) mouse (8 to 64 weeks old) brain sections were imaged using the three magnification levels and A-β plaques ranging from 10 to 70 μm in diameter were observed in the cortex

  • Our results suggest that mouse brain tissue exhibits a higher plaque load when compared with human brain tissue in the cortex

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Summary

Introduction

One out of nine Americans aged above 65 years is suffering from Alzheimer’s disease (AD), making it the most common form of dementia worldwide.[1] As our society is facing an aging population, the cases of AD will double in the 20 years, leading to a considerable financial and social burden. Patients are losing their ability to remember and in the end are dependent on care-giving.[1] To diagnose AD while the patient is still alive, clinicians have to exclude other diseases with similar symptoms and check for cognitive and behavior changes with neurophysological tests. AD can only be diagnosed by a histological analysis of the brain tissue postmortem. As a step toward treatment of the disease, an early diagnosis is crucial.[2]

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