ApoE allelic variability influences pupil response to cholinergic challenge and cognitive impairment

Abstract

Exaggerated pupil response to dilute tropicamide has been suggested as an early biological marker for Alzheimer’s disease. The current study links apolipoprotein E (ApoE) allelic variability to the magnitude of pupil response in a sample of community‐dwelling elderly without a diagnosis of Alzheimer’s disease or dementia. Possession of an ɛ4 allele influences both the likelihood of exhibiting an exaggerated pupil response above a predetermined cut‐off (13% above baseline diameter) and the absolute overall magnitude of the response. Allelic variability was also shown to correlate with cognitive impairments in memory and attention. The data in this study further elucidate the nature of the biological bond between an exaggerated pupil response and the pathology of Alzheimer’s disease. ApoE allelic variability is probably linked to pupil response through its influence on tau hyperphosphorylation. The early Alzheimer’s pathology seen in the Edinger–Westphal area of cranial nerve III, a major centre for pupil control, is primarily tau‐based with significant cell loss in this nucleus leading to central denervation hypersensitivity even in elderly who are clinically silent but who have early pathology.

Visual and Ocular Manifestations of Alzheimer’s Disease and Their Use as Biomarkers for Diagnosis and Progression

“…Subsequent experiments by Iijima et al ( 68 ) found that significant differences in pupil sizes were found at a lower dose of tropicamide (0.005%), potentiating the possibility for a diagnostic screening test. Scinto ( 69 ) further investigated pupil involvement in AD and located a clear biological link between ApoE allele status and pupillary response to dilute tropicamide. Nevertheless, the use of the tropicamide test as a diagnostic tool for AD is controversial, as other studies have failed to find significant results ( 70 – 72 ).…”

Alzheimers Disease and Retinal Neurodegeneration

“…Recently, Scinto showed that Apolipoprotein E (ApoE) allelic variability, a factor linked to late-onset, sporadic AD [52,53], influences pupil response to cholinergic challenge via tau hyperphosphorylation [54]. Furthermore, Scinto reported in a prospective longitudinal study that there is an increased risk with a hypersensitive pupil response for developing significant cognitive impairment in areas of memory attention and language in a pattern that is consistent with pre-clinical AD, and the risk is even higher with ApoE allelic variability [55].…”

Cognitive dysfunctions in high myopia: An overview of potential neural morpho-functional mechanisms

“…The STS is associated with a variety of brain regions linked with the processing of social information ( 77 – 82 ). It has been found that parts of the STS respond to specific visual and auditory stimuli Including facial expression and gaze ( 83 – 93 ), bodies ( 16 , 17 , 80 , 88 ), point-light walkers ( 15 , 68 , 79 , 89 , 90 ), human voices ( 20 , 91 ), language ( 21 , 92 ), and the audiovisual integration of speech ( 22 , 93 ). Furthermore, the temporoparietal junction (TPJ) which lies posterior and superior to the STS controls theory of mind tasks ( 94 ), in which participants interpret the actions of characters in stories.…”