A study recently published in Acta Neuropathologica, led by investigators from the Cedars-Sinai Medical Center in Los Angeles, California, identified and mapped retinal changes caused by Alzheimer’s disease (AD) and mild cognitive impairment (MCI).
Give me some background.
It is known to be difficult to detect and clinically monitor AD during earlier stages when neuronal damage is limited. However, as a developmental extension of the brain unshielded by bone, the retina offers unparalleled accessibility for direct, affordable, and noninvasive visualization and temporal monitoring of the central nervous system (CNS).
Experts believe that understanding the connection between retinal degeneration and early-stage AD is key to developing more effective treatments that could prevent progression.
Talk about the study.
Investigators conducted an exploratory histopathological and biochemical investigation of postmortem retina and brain tissue samples from 86 human donors collected over 14 years.
A quantitative examination of the retinas of patients with MCI, AD, and later-stage AD dementia was performed and then compared to those with normal cognition (NC).
They also measured and mapped markers of inflammation and functional cell loss and performed a proteome analysis by mass spectrometry to analyze the proteins in retinal and brain tissues.
What were the results?
Key retinal pathologies that investigators identified in patients with MCI and AD include an overabundance of the protein amyloid beta 42 (Aβ42). In AD patients, this protein clumps together to form plaques that disrupt brain function and accumulation of amyloid beta protein in ganglion cells, which bridge visual input from the retina to the optic nerve.
Investigators also noted a higher number of astrocytes and immune cells (called microglia) that tightly surround amyloid beta plaques; as many as 80% fewer microglial cells clearing amyloid beta proteins from the retina and brain; and specific molecules and biological pathways responsible for inflammation and cell and tissue death.
Let’s dissect this.
The retinal changes investigators identified above “correlated with changes in parts of the brain called the entorhinal and temporal cortices, a hub for memory, navigation, and the perception of time,” according to Maya Koronyo-Hamaoui, PhD, senior author of the study.
Further, the retinal changes correlated with the pathological stage of AD (using theBraak staging system) and patients’ cognitive status. They were found even in patients who appeared cognitively normal or very mildly impaired by AD.
The investigators highlighted how the research points to the potential of using retinal biomarkers to develop imaging techniques that would allow clinicians to “diagnose AD earlier and more accurately monitor its progression noninvasively by looking through the eye.”