title: 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 epsilon 4 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.
authors.affiliation: Laboratory of Higher Cortical Functions, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. leonard_scinto@hms.harvard.edu
authors.forename: L F M
authors.initials: LF
authors.lastname: Scinto
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D001288:Attention / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics*; D004106:Dilatation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009184:Mydriatics / Q000008:administration & dosage; D009883:Ophthalmic Solutions; D011680:Pupil / Q000187:drug effects*; D012016:Reference Values; D014331:Tropicamide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D053327:Apolipoprotein E4; D018727:Muscarinic Antagonists; D009184:Mydriatics; D009883:Ophthalmic Solutions; D014331:Tropicamide