Eyes Provide Peek at Alzheimer’s Disease Risk

Protein deposits in retina and brain appear to parallel possible neurodegeneration, an insight that might lead to easier, quicker detection. Amyloid plaques are protein deposits that collect between brain cells, hindering function and eventually leading to neuronal death. They are considered a hallmark of Alzheimer’s disease (AD), and the focus of multiple investigations designed to reduce or prevent their formation, including the nationwide A4 study.

But amyloid deposits may also occur in the retina of the eye, often in patients clinically diagnosed with AD, suggesting similar pathologies in both organs. In a small, cross-sectional study, a team of researchers, led by scientists at University of California San Diego School of Medicine, compared tests of retinal and brain amyloids in patients from the A4 study and another study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration) assessing neurodegeneration risk in persons with low levels of amyloid.

Like the proverbial “windows to the soul,” the researchers observed that the presence of retinal spots in the eyes correlated with brain scans showing higher levels of cerebral amyloid. The finding suggests that non-invasive retinal imaging may be useful as a biomarker for detecting early-stage AD risk.

Amyloid deposits tagged by curcumin fluoresce in a retinal scan.

This was a small initial dataset from the screening visit. It involved eight patients,” said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine. “But these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD — a preclinical diagnosis — using retinal imaging, rather than more difficult and costly brain scans. We look forward to seeing the results of additional timepoint retinal scans and the impact of solanezumab (a monoclonal antibody) on retinal imaging. Unfortunately we will need to wait to see and analyze these data when the A4 trial is completed.”

The findings published in the journal Alzheimer’s & Dementia.

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Rare genetic mutation holds clues to preventing Alzheimer’s

Could one woman’s rare genetic mutation one day have a global impact on dementia risk? It’s possible, say investigators who report on a potentially groundbreaking case of a woman whose genetic mutation staved off dementia for decades, even though her brain had already been damaged by Alzheimer’s disease. While most Alzheimer’s cases are not driven by genetic predisposition, one woman in Colombia is among about 1,200 in her country who do face a genetically higher risk for early-onset Alzheimer’s. Why? They all carry the E280A mutation of a gene called Presenilin 1 (PSEN1), which is known to increase the chances for Alzheimer’s at a far younger age than usual.

We identified an individual that was predisposed to develop Alzheimer’s in her 40s,” noted study author Dr. Joseph Arboleda-Velasquez. He’s an assistant professor of ophthalmology with the Schepens Eye Research Institute of Mass Eye and Ear at Harvard Medical School, in Boston.

But, strangely, the woman “remained unimpaired until her 70s,” Arboleda-Velasquez added. The twist: the woman had, in fact, developed clear telltale signs of Alzheimer’s in her brain. She just hadn’t developed dementia. For example, while she had fewer neural “tangles” in her brain than is typical for Alzheimer’s patients, by the time she hit her 40s she did have the same unusually high level of brain amyloid-beta deposits as her E280A peers. Such deposits are a key signature of Alzheimer’s. So why didn’t she develop middle-aged dementia like her peers?

To unravel the mystery, Arboleda-Velasquez and his colleagues ran an in-depth genetic analysis on the woman. And what they found is that she had not just one mutation, but two. In addition to the E280A mutation, she also carried the so-calledChristchurchmutation in the APOE3 gene. But there’s more. Not only did she carry the Christchurch mutation, but she had two of them. Some of her E280A peers (about 6%) also carried a single copy of Christchurch. But she was the only one who carried two, the investigators found. “It is ultra-rare, with an approximate prevalence of less than one in every 200,000 individuals,” Arboleda-Velasquez said.

And having one such rare mutation did not appear to be enough. No protection against dementia was linked to only one Christchurch mutation. But as this woman’s case suggests, having two such mutations did seem to throw up a shield against Alzheimer’s, preserving her ability to remember things and think clearly for a few decades, long after her E280A peers had started experiencing cognitive decline.

Source: https://www.cbsnews.com/

Eye Test Reveals How Likely Is A Person To Develop Alzheimer’s

Alzheimer’s disease (AD) begins to alter and damage the brain years — even decadesbefore symptoms appear, making early identification of AD risk paramount to slowing its progression.

In a new study published online in the September 9, 2019 issue of the Neurobiology of Aging , scientists at University of California San Diego School of Medicine say that, with further developments, measuring how quickly a person’s pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increased genetic risk for AD before cognitive decline begins.

In recent years, researchers investigating the pathology of AD have primarily directed their attention at two causative or contributory factors: the accumulation of protein plaques in the brain called amyloid-beta and tangles of a protein called tau. Both have been linked to damaging and killing neurons, resulting in progressive cognitive dysfunction.

The new study focuses on pupillary responses which are driven by the locus coeruleus (LC), a cluster of neurons in the brainstem involved in regulating arousal and also modulating cognitive function. Tau is the earliest occurring known biomarker for AD; it first appears in the LC; and it is more strongly associated with cognition than amyloid-beta. The study was led by first author William S. Kremen, PhD, and senior author Carol E. Franz, PhD, both professors of psychiatry and co-directors of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine.

The LC drives pupillary response — the changing diameter of the eyes’ pupils — during cognitive tasks. (Pupils get bigger the more difficult the brain task.) In previously published work, the researchers had reported that adults with mild cognitive impairment, often a precursor to AD, displayed greater pupil dilation and cognitive effort than cognitively normal individuals, even if both groups produced equivalent results. Critically, in the latest paper, the scientists link pupillary dilation responses with identified AD risk genes.

face of an elderly man

How quickly a person’s pupils dilate while doing mental tasks may be an indicator of increased genetic risk for Alzheimer’s disease.

Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual’s inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer’s before symptom appear,” said Kremen.

Source: https://health.ucsd.edu/