Monitoring Alzheimer’s Disease via Ultraweak Photon Emission
Authors: Sefati Niloofar , Esmaeilpour Tahereh , Salari Vahid , Zarifkar Asadollah , Dehghani Farzaneh , Khorsand Ghaffari Mahdi , Császár Noémi , Bókkon István , Rodrigues Serafim , Oblak Daniel 
Published: March 2023

ABSTRACTThe present study takes on an innovative experiment involving detection of ultraweak photon emission (UPE) from the hippocampus of male rat brains and finds significant correlations between Alzheimer’s disease (AD), memory decline, oxidative stress, and the intensity of UPE emitted spontaneously from the hippocampus. These remarkable findings opens up novel methods for screening, detecting, diagnosing and classifying neurodegenerative diseases (and associated sydromes), such as in AD. This also paves the way towards novel advanced brain-computer interfaces (BCIs) photonic chip for the detection of UPE from brain’s neural tissue. The envisaged BCI photonic chip (BCIPC) would be minimally invasive, cheap, high-speed, scalable, would provide high spatiotemporal resolution of brain’s activity and would provide short- and long-term screening of clinical patho-neurophysiological signatures, which could be monitored by a smart wristwatch or smartphone via a wireless connection.Background & aimLiving cells spontaneously emit biophotons, or UPE, during the process of metabolic reactions, and these UPE in tissues may be altered in pathological conditions. These compelling observations led us to hypothesise that AD (a severe neuropathological disorder) can be screened via UPE. This is substantiated by previous studies showing that oxidative stress occurs prior to the formation of amyloid plaques and neurofibrillary tangles (i.e. the neuropathological hallmarks of AD). Indeed, oxidative stress is a critical factor contributing to the initiation and progression of AD. Moreover, earlier research have evidenced the association between UPE and oxidative stress of biological tissue. These combined observations set us to investigate whether UPE intensity of the hippocampus in a pathological state, induced by intracerebroventricular (ICV) injection of streptozotocin (STZ), can be correlated with memory, oxidative stress, Acetylcholinesterase (AChE) as a novel screening strategy for AD.Material & methodsThirty-two adult male rats were divided into four groups: Control, Sham, STZ, and STZ+Donp (n=8). Specifically, for inducing sporadic AD (sAD), STZ was injected on days 1 and 3. One week after the second ICV injection, the intraperitoneal (IP) use of donepezil was initiated and continued for two weeks. After treatment, spatial and recognition memory were evaluated from days 24 to 29 of the experiment using the Morris water maze (MWM) and novel object recognition (NOR) test, respectively. Finally, the rats were euthanased by cervical dislocate in day 30. Anesthetic drugs disrupt neural communication from chemical neurotransmitter receptor inhibition. UPE related to cells activity so anesthesia intervention must be considered. Then, their brains were removed and the hippocampus dissected. The Right hippocampus was evaluated in terms of UPE via a Photomultiplier tubes (PMT) device. Moreover, in left hippocampus we measured malondialdehyde (MDA) by the TBARS assay and heat via calorimeter ELIZA device. Acetylcholinesterase (AChE) activity was also scrutinized via acetylthiocholine reaction via the Ellman method.Results & discussionSTZ injection impaired learning and memory function compared with the sham and control groups. The results of the MWM test indicated a decrease in the time used to find the hidden platform in the donepezil-treated group during training days, while in the STZ group, no significant reduction in this time was observed. In the probe trial, the donepezil-treated group showed a significant increase in target quadrant time in comparison with the STZ group (p<0.05). Furthermore, the object recognition test demonstrated that the donepezil-treated group spent more time recognizing new objects in the testing phase (p<0.05). Whereas, in the STZ group, there was no significant difference in spent time for identifying the objects. Ex vivo detection of UPE from the hippocampus of rats showed that the sham group had higher UPE than the Control group (p<0.05). The STZ injection significantly increased UPE and MDA concentrations in the hippocampus than in the Sham and Control groups (p<0.0001). Correlation analysis of results reveal that the emission intensity is associated with the MDA concentration (r = 0.855). Hippocampus AChE activity also significantly increased in STZ-injected groups. Treatment with donepezil decreased MDA concentration, UPE intensity, and activity of AChE in comparison with the STZ group (p<0.05). UPE intensity was linked with AChE activity as evidenced by Pearson correlation analysis between UPE intensity and AChE activity (r = 0.779). Conclusion: The hippocampus UPE increases in STZ-induced sAD and is associated with the redox state of the tissue. Donepezil decreases the UPE and improves the oxidative stress induced by STZ injection. Since oxidative stress is one of the primary hallmarks in the progression of AD, then it stands to reason that the Brain’s UPE emission can be used as a novel methodology for screening AD. Moreover, UPE could be used to monitor recovery from neurodegenerative diseases upon suitable future therapeutic treatments, as suggested by our experiment involving donepezil. Our findings, encourages further research and suggests the development of a minimally invasive BCI photonic chip (with similar quantum efficiency as PMT) for screening and diagnosing AD.