A discovery beyond the Hippocampus could hold the key to early Alzheimer's diagnosis
Lost keys yet again? Having trouble remembering locations at home? When these happen too often, it may not be wise to dismiss it all as a natural part of aging. Researchers at RIKEN Brain Institute in Japan may have found a biomarker for diagnosing Alzheimer's Disease (AD) after investigating the Medial (middle) Entorhinal Cortex (MEC), essential for memory in young mice (3-5 months old). MEC is separate from the hippocampus (HC). The research shows that neuronal firing may degrade, causing miscoordination between the MEC & HC and is the primary cause of memory impairments in AD.
In healthy brains when multiple neurons fire in synchrony, an EEG (used to record brain activity) creates a visible pattern. MEC Grid neurons can remap, having distinct firing in different environments. CA1 is a hippocampal area coding for space. An MEC neuron network generates Sharp Wave Ripples (SWR), characterized by their high frequency and short duration activity pattern, enabling memory consolidation. When more neurons are involved, more information is carried between the MEC & CA1, and the longer these SWRs are, higher is the spatial information consolidation. The CA1 and the MEC are bidirectionally connected allowing for MEC SWRs to contribute to generating CA1 SWRs too.
Simultaneous MEC & CA1 EEGs were recorded, as a small group of mice (n=12) completed a maze task. For 5 days, 2 groups of preclinical mice - one control and another exhibiting Alzheimer’s symptoms (APP-KI) both ran on 2 tracks in succession. Track A had black rubber floors and white boards enclosed in black and Track B had white sandpaper floors with clear black boards enclosed in white. On the last day researchers collected combined data across both tracks.
While long SWRs decreased in CA1 within APP-KI mice, other SWR properties were comparable across MEC & CA1 indicating specific pathology within the CA1. Generation of MEC SWRs was intact which contrasted with delayed CA1 SWRs in the APP-KI mice. These occurred after the MEC rather than before, in control mice. Affected propagation of SWRs from MEC to CA1 in AD could thus lead to SWR event coordination disruption between MEC & CA1. These findings indicate that an absence of SWRs due to neuronal miscommunication could precede memory problems in AD. However, more research is needed with explicit translational outcomes. Coordination of Entorhinal SWRs within early life could be a network symptom and biomarker for early AD diagnosis preceding memory impairment.
References
Funane, T., Jun, H., Sutoko, S., Saido, T. C., Kandori, A. and Igarashi, K. M. 2022. Impaired sharp wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock in model of Alzheimer’s disease. Frontiers in Systems Neuroscienc e 16, p. 955178. doi: 10.3389/fnsys.2022.955178