Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease


Autoři: Angela J. Oh aff001;  Giulia Amore aff001;  William Sultan aff001;  Samuel Asanad aff001;  Jason C. Park aff003;  Martina Romagnoli aff002;  Chiara La Morgia aff002;  Rustum Karanjia aff001;  Michael G. Harrington aff006;  Alfredo A. Sadun aff001
Působiště autorů: Doheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America aff001;  IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy aff002;  Columbia University, Department of Psychology, New York, New York, United States of America aff003;  Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy aff004;  University of Ottawa Eye Institute, Department of Ophthalmology, Ottawa, Ontario, Canada aff005;  The Huntington Medical Research Institutes and Molecular Neurology Program, Pasadena, California, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226197

Souhrn

Background

Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD.

Methods

We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm.

Results

Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls.

Conclusions

The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

Klíčová slova:

Alzheimer's disease – Circadian rhythms – Cognitive impairment – Chronobiology – Light – Retinal ganglion cells – Sleep


Zdroje

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2019 Číslo 12