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How the eyes might be windows to the risk of Alzheimer’s disease – Research

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Alzheimer’s disease (AD) begins to alter and damage the brain years -- even decades -- before 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, lowinvasiv­e 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.

“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.

 ?? PHOTO: ?? Blue patches show how webs of tiny blood vessels at the back of the eye are less dense in an Alzheimer’s patient (right) compared with a healthy individual (Duke Eye Center/PA) Duke Eye Center
PHOTO: Blue patches show how webs of tiny blood vessels at the back of the eye are less dense in an Alzheimer’s patient (right) compared with a healthy individual (Duke Eye Center/PA) Duke Eye Center
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