Changes in the blood vessels of the eye: A new window into Alzheimer’s diagnosis

Summary: Abnormalities in eye blood vessels can provide early diagnosis of Alzheimer’s disease. By comparing blood vessels in the retina of Alzheimer’s patients, individuals with mild cognitive impairment, and healthy subjects, the team discovered a disruption of the blood-retinal barrier, which prevents harmful substances from entering the retinal tissue.

This disorder, observed even in patients with only mild functional impairment, correlates strongly with cerebral amyloid angiopathy (CAA), a condition associated with Alzheimer’s disease. The findings suggest that monitoring changes in ocular blood vessels may offer a non-invasive route to early detection and tracking of Alzheimer’s progression.

Key facts:

1. Disruption of the blood-retinal barrier, which allows harmful substances to penetrate the retinal tissue, is seen as an early sign of Alzheimer’s disease.
2. Impairment of the blood-retinal barrier is strongly associated with cerebral amyloid angiopathy (CAA) and other vascular diseases in the brain.
3. Advanced retinal imaging currently being developed can non-invasively monitor these changes in the blood vessels of the eyes to detect Alzheimer’s disease in living patients.

source: Cedars-Sinai Medical Center

Blood vessel abnormalities in the eye are a major factor in the progression of Alzheimer’s disease, according to a study by Cedars-Sinai researchers published in the journal Alzheimer’s and dementia.

These changes correspond to changes in the brain, offering a new opportunity for early diagnosis.

“This study provides new understanding of the vascular changes associated with Alzheimer’s disease, particularly in the retina, the layer of nerve tissue at the back of the eye,” said Maya Koronio-Hamaoui, PhD, professor of neurology, neurosurgery and biomedical sciences at Cedars- Sinai and senior author of the study.

“It also pinpoints the damage that Alzheimer’s disease causes to blood vessels in the retina, allowing a new, non-invasive route to early diagnosis and tracking the progression of the disease.”

The researchers compared retinal blood vessels collected from 24 human donors with Alzheimer’s disease, 10 donors with mild cognitive impairment and 27 with normal cognitive abilities.

In patients with Alzheimer’s disease and mild cognitive impairment, they found one of the earliest signs of Alzheimer’s disease to date: a breakdown of the blood-retinal barrier, where tight-knit cells prevent harmful substances from entering the retinal tissue.

“In patients with Alzheimer’s disease, we found that there is a deficiency of as much as 70% in this barrier, which means that harmful substances can pass through and enter the retinal tissue,” said Haoshen Shi, M.D., Ph.D., a scientist on the project and first author of the study. “We see this happening very early, in patients with only mild functional impairment.”

Damage to the blood-retinal barrier is strongly associated with a condition called cerebral amyloid angiopathy (CAA) — the accumulation of amyloid proteins in small blood vessels — and other vascular diseases in the brain.

“Currently, the only way to detect CAA in patients is in post-mortem brain tissue samples,” Coronio-Hamaoui said. “With further research and the development of advanced retinal imaging, damage to the vascular and blood-retinal barrier may give us the first opportunity to detect CAA in living patients.”

The study also found that deposits of a protein called amyloid beta 40 build up in the retinal arteries of Alzheimer’s patients, making the arteries stiff, disrupting blood flow and preventing the arteries from clearing harmful substances from the retina.

Further studies are needed to determine whether the deposits build up due to damage to the blood vessels or actually cause the damage, Coronio-Hamaoui said.

“Retinal and brain tissues are rich in blood vessels, and a high blood supply is fundamental to their function,” Coronio-Hamaoui said. “The restriction of blood supply that can occur because of the damage that we show is happening here means that these cells are not getting the oxygen and nutrients that they need.”

Advanced retinal imaging, which would look at blood vessels and protein deposits noninvasively in living patients, is in development but has not yet been approved by the Food and Drug Administration, Coronio-Hamaoui said.

“As an anatomical extension of the brain, the retina has been extensively studied as a window into disorders of the central nervous system,” said Keith L. Black, MD, chairman of the Department of Neurosurgery and the Ruth and Lawrence Harvey Endowed Chair in Neuroscience at Cedars-Sinai.

“This work complements recent advances in advanced retinal imaging and the identification of other retinal biomarkers to advance the science of early detection of Alzheimer’s disease.”

In the meantime, Koronyo-Hamaoui advises people to do what they can to keep their circulatory system, including blood vessels in the retina and brain, healthy to prevent CAA and dementia.

“Controlling hypertension, eating a healthy, low-sugar diet, reducing alcohol consumption and avoiding smoking help prevent chronic inflammation and blood vessel damage,” Coronio-Hamaoui said. “Our study shows that blood vessel damage is a major element in the progression of Alzheimer’s disease.”

For this Alzheimer’s research news

Author: Christina Elston
source: Cedars-Sinai Medical Center
Contact: Christina Elston – Cedars Sinai Medical Center
Image: Image credited to Neuroscience News

Original Research: Free access.
“Retinal Aβ 40 deposition is associated with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients” by Haoshen Shi et al. Alzheimer’s and dementia

Summary

Retinal Aβ 40 deposition is associated with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients

INTRODUCTION

Vascular amyloid beta (Aβ) protein deposits were found in the retina of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We tested the hypothesis that retinal vascular tight junctions (TJs) are compromised and associated with disease status.

METHODS

TJ components and Aβ expression in capillaries and larger blood vessels were determined in posthumously the retinas of 34 patients with MCI or AD and 27 cognitively normal controls and correlated with neuropathology.

RESULTS

Severe decreases in retinal vascular zone occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aβ₄₀ postponement has been identified in MCI and AD patients. Retinal claudin-5 deficiency is closely associated with cerebral amyloid angiopathy, while ZO-1 defects correlate with cerebral pathology and cognitive deficits.

DISCUSSION

We identified deficiencies in blood-retinal barrier markers for potential targets for retinal imaging in AD screening and monitoring. Intense retinal arteriolar Aβ₄₀ deposition suggests a common pathogenic mechanism of failed Aβ clearance by intramural periarterial drainage.