In Vivo Assessment of Retinal Biomarkers by Hyperspectral Imaging: Early Detection of Alzheimer’s Disease

Abstract Studies of rodent models of Alzheimer’s disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.

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P1-174: Early detection of β-amyloid aggregation in in vivo and in vitro models of Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2010.05.724 ◽

2010 ◽

Vol 6 ◽

pp. S224-S224 ◽

Cited By ~ 1

Author(s):

Louise A. Scrocchi ◽

Elizabeth Karaskov ◽

Vivian Lee ◽

Hui Chen ◽

Melissa Osborne ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Detection ◽

In Vitro Models ◽

Amyloid Aggregation ◽

Β Amyloid

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P4-116: DIRECT IN VIVO ASSESSMENT OF SEX-RELATED METABOLIC DIFFERENCES IN A MOUSE MODEL OF ALZHEIMER'S DISEASE BY MRI

Alzheimer s & Dementia ◽

10.1016/j.jalz.2014.05.1632 ◽

2014 ◽

Vol 10 ◽

pp. P826-P826

Author(s):

A. Alia ◽

Sara van Duijn ◽

Firat Kara ◽

Mark van Buchem

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Model Of Alzheimer’S Disease ◽

In Vivo Assessment

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ELECTRORETINOGRAPHY IN PRE-CLINICAL ALZHEIMER’S DISEASE: AN ELECTROPHYSIOLOGIC ASSESSMENT OF THE RETINA AS AN EARLY DETECTION OCULAR BIOMARKER IN VIVO

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.4847 ◽

2019 ◽

Vol 15 (7) ◽

pp. P1619-P1620

Author(s):

Christian Felix ◽

Samuel Asanad ◽

Rustum Karanjia ◽

Alfredo A. Sadun ◽

Michael G. Harrington

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Detection

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Retinal hyperspectral imaging in the 5xFAD mouse model of Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-021-85554-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeremiah K. H. Lim ◽

Qiao-Xin Li ◽

Tim Ryan ◽

Phillip Bedggood ◽

Andrew Metha ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Hyperspectral Imaging ◽

Screening Tools ◽

Hyperspectral Reflectance ◽

Model Of Alzheimer’S Disease ◽

Reflectance Profile

AbstractHyperspectral imaging of the retina has recently been posited as a potentially useful form of spectroscopy of amyloid-beta (Aβ) protein in the eyes of those with Alzheimer’s disease (AD). The concept of using the retina as a biomarker for AD is an attractive one, as current screening tools for AD are either expensive or inaccessible. Recent studies have investigated hyperspectral imaging in Aβ models however these studies have been in younger mice. Here we characterised hyperspectral reflectance profile in 6 to 17 months old 5xFAD mice and compare this to Aβ in isolated preparations. Hyperspectral imaging was conducted across two preparations of Aβ using a custom built bench ophthalmoscope. In the in vitro condition, 1 mg of purified human Aβ42 was solubilised and left to aggregate for 72 h. This soluble/insoluble Aβ mixture was then imaged by suspending the solution at a pipette tip and compared against phosphate buffered saline (PBS) control (n = 10 ROIs / group). In the in vivo condition, a 5xFAD transgenic mouse model was used and retinae were imaged at the age of 6 (n = 9), 12 (n = 9) and 17 months (n = 8) with age matched wildtype littermates as control (n = 12, n = 13, n = 15 respectively). In the vitro condition, hyperspectral imaging of the solution showed greater reflectance compared with vehicle (p < 0.01), with the greatest differences occurring in the short visible spectrum (< 500 nm). In the in vivo preparation, 5xFAD showed greater hyperspectral reflectance at all ages (6, 12, 17 months, p < 0.01). These differences were noted most in the short wavelengths at younger ages, with an additional peak appearing at longer wavelengths (~ 550 nm) with advancing age. This study shows that the presence of Aβ (soluble/insoluble mixture) can increase the hyperspectral reflectance profile in vitro as well as in vivo. Differences were evident in the short wavelength spectrum (< 500 nm) in vitro and were preserved when imaged through the ocular media in the in vivo conditions. With advancing age a second hump around ~ 550 nm became more apparent. Hyperspectral imaging of the retina does not require the use of contrast agents and is a potentially useful and non-invasive biomarker for AD.

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In vivo assessment of the noradrenergic nucleus locus coeruleus in Alzheimer’s disease and other types of dementia

Alzheimer s & Dementia ◽

10.1002/alz.043616 ◽

2020 ◽

Vol 16 (S5) ◽

Author(s):

Filippo Sean Giorgi ◽

Alessandro Galgani ◽

Francesco Lombardo ◽

Giovanni Palermo ◽

Hlavata Hana ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Locus Coeruleus ◽

In Vivo Assessment

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Biological markers for early detection and pharmacological treatment of Alzheimer's disease

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2009.11.2/hhampel ◽

2009 ◽

Vol 11 (2) ◽

pp. 141-157 ◽

Cited By ~ 5

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Detection ◽

Biological Markers ◽

Molecular Mechanisms ◽

Diagnostic Process ◽

Innovative Drug ◽

Treatment Benefits ◽

Drug Treatments

The introduction of biological markers in the clinical management of Alzheimer's disease (AD) will not only improve diagnosis relating to early detection of neuropathology with underlying molecular mechanisms, but also provides tools for the assessment of objective treatment benefits. In this review, we identify a number of in vivo neurochemistry and neuroimaging techniques, which can reliably assess aspects of physiology, pathology, chemistry, and neuroanatomy of AD, and hold promise as meaningful biomarkers in the early diagnostic process, as well as for the tracking of disease-modifying pharmacological effects. These neurobiological measures appear to relate closely to pathophysiological, neuropathological, and clinical data, such as hyperphosphorylation of tau, abeta metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal integrity, and functional and cognitive decline, as well as risk of future decline. As a perspective, the important role of biomarkers in the development of innovative drug treatments for AD and the related regulatory process is discussed.

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