Pupil response biomarkers distinguish amyloid precursor protein mutation carriers from non-carriers

Document Type

Journal Article

Keywords

Alzheimer's, Amyloid, Autosomal, Eye, Pupilamyloid precursor protein, biological marker, adult, Alzheimer disease, area under the curve, article, Australia, autosomal dominant inheritance, brain function, clinical article, controlled study, early diagnosis, family, female, gene mutation, heterozygote, human, male, medical research, mutation, priority journal, pupil flash response, pupil reflex, pupillometry, sensitivity and specificity, Adult, Alzheimer Disease, Amyloid beta-Protein Precursor, Biological Markers, Early Diagnosis, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Pupil

Publisher

Bentham Science Publishers Ltd

Faculty

Faculty of Health, Engineering and Science

School

School of Medical Sciences / Centre of Excellence for Alzheimer's Disease Research and Care

RAS ID

16861

Comments

Frost, S., Kanagasingam, Y., Sohrabi, H. R., Taddei, K. , Bateman, R., Morris, J., Benzinger, T., Goate, A., Masters, C., & Martins, R. N. (2013). Pupil Response Biomarkers Distinguish Amyloid Precursor Protein Mutation Carriers from Non-Carriers. Current Alzheimer Research, 10(8), 790-796. Available here

Abstract

Context: Alzheimer's disease (AD) is usually only diagnosed many years after pathology begins. Earlier detection would allow emerging interventions to have a greater chance to preserve healthy brain function. A rare form of Alzheimer's disease, caused by autosomal-dominant mutations, affects carriers with 100% certainty and at a younger age specific to their mutation. Studying families with these mutations allows a unique investigation of the temporal sequence of biomarker changes in Alzheimer's disease. Objective: To determine whether the pupil flash response (PFR), previously reported to be altered in sporadic Alzheimer's disease, is different in pre-symptomatic mutation carriers. Design: Researchers blinded to participant mutation status collected pupil response data from cognitively normal participants in the Dominantly Inherited Alzheimer's Network (DIAN) Study during 2010-2011. Setting: The pupil response was examined at the McCusker Alzheimer's Research Foundation in Perth, Western Australia. Participants: Participants were from a single family harboring an Amyloid-Beta Precursor Protein genetic mutation (APPGlu693Gln). Six carriers and six non-carriers were available for pupil testing (age 43.0±8.3 years old, 2 males and 10 females, 4 with hypertension). Main Outcome Measure: Pupil response parameter comparison between mutation carriers and non-carriers. Results: 75% recovery time was longer in mutation carriers (p<0.0003, ROC AUC 1.000, Sensitivity 100%, Specificity 100%) and percentage recovery 3.5 seconds after stimulus was less in mutation carriers (p<0.006, ROC AUC 1.000, Sensitivity 100%, Specificity 100%). Conclusions: PFR changes occur pre-symptomatically in autosomal dominant AD mutation carriers, supporting further investigation of PFR for early detection of AD.

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Link to publisher version (DOI)

10.2174/15672050113109990154